Lung Tissue Malondialdehyde Research Articles

Hesperetin alleviates pulmonary injury in a blunt chest trauma-induced pulmonary contusion model in rats

Pulmonary contusion (PC), a condition that occurs frequently in severe thoracic injuries, is a significant contributor to mortality in those under the age of 40. Hesperetin, a natural flavonoid derivative of hesperidin, is a substance found in various citrus fruits such as oranges and grapefruits and possesses a variety of biological activities, including antiapoptotic, antioxidant, and anticancer effects. In the current study, we investigated the effect of hesperetin on pulmonary tissue structure, expression of some pro-inflammatory cytokines, and mediators in a PC model induced by blunt chest trauma. In this study, 18 adult male Wistar albino rats (8 – 10 weeks, 250 – 300 g) were used. The rats were divided into three groups: control, PC, and PC + hesperetin. Hesperetin administration (100 mg/kg/day oral) was completed for 7 days following induction of the model. The wet/dry weight ratio of pulmonary tissue was determined. Tumor necrosis factor alpha (TNFα) and malondialdehyde (MDA) in lung tissues, serum interleukin (IL)-6, and IL-1β levels were determined using the enzyme-linked immunosorbent assays. Pulmonary tissue specimens were examined histologically using hematoxylin-eosin and Masson trichrome staining. Inducible nitric oxide synthase (iNOS) activity was determined using immunohistochemical methods. Hesperetin administration reduced TNFα and iNOS activity, serum IL-1β, IL-6, MDA, and wet/dry weight ratio in pulmonary tissue to improve pulmonary function. Our results showed that administration of hesperetin prevents activation of local inflammatory mediators, thereby obstructing the proinflammatory cytokine cascade and tissue injury.

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway

Ethnopharmacological relevanceHuangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe “Huangqi Baihe porridge” and the Dunhuang medical prescription “Cistanche Cistanche Soup.” The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments. Aim of the studyThe purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules. Materials and methodsThe HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR. ResultsHQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines. ConclusionsHQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

Effects of alamandine on monocrotaline-induced pulmonary hypertension in rats.

Pulmonary arterial hypertension (PAH) is a severe and often fatal disease that is associated with oxidative stress and inflammation. Alamandine, a component of the renin-angiotensin system, known for its antioxidative, anti-inflammatory, and antifibrotic effects, has been investigated in this study to determine if it has protective effects against PAH induced by monocrotaline (MCT) and if these effects are associated with oxidative stress, inflammatory factors, and inducible nitric oxide synthase (iNOS). Rats were administered MCT (40 mg/kg) on day 0 and then received alamandine (50 mg/kg/day) via mini-osmotic pumps for 21 days starting one day later. Hemodynamic parameters, electrocardiograms, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), inflammatory cytokines (TNF-α, IL-1β, and NF-κB), iNOS, and MrgD receptor expression in lung tissue were evaluated at the end of the 21-day period. The MrgD receptor was quantified through immunofluorescent staining, and the histopathology of lung tissues was evaluated using hematoxylin and eosin staining. The results showed that alamandine treatment significantly improved hemodynamic parameters, oxidative stress markers, inflammatory factors, and electrocardiographic data. Furthermore, treatment with alamandine decreased the levels of iNOS. Additionally, alamandine treatment decreased the expression levels of MrgD receptors in the lung tissue of MCT-induced PAH. In summary, this study indicates that alamandine has protective effects against monocrotaline-induced PAH, and these effects may be attributed to the inhibition of oxidative stress, inflammatory parameters, and iNOS.

Codonopsis Radix Inhibits the Inflammatory Response and Oxidative Stress in Chronic Obstructive Pulmonary Disease Mice through Regulation of the Nrf2/NF-κB Signaling Pathway

Introduction: Chronic obstructive pulmonary disease (COPD) is a nonspecific chronic inflammatory lung disease with no known cure. Codonopsis Radix (CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR varieties on COPD mice. Methods: Sixty male-specified pathogen-free grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract combined with lipopolysaccharide, and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin, Masson, and periodic acid-Schiff stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an ELISA. Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking were used to predict signaling pathways, which were validated by Western blot analysis. Results: Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (p < 0.01). Western blot analysis also indicated significant downregulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant upregulation of Nrf2 protein expression in the lung tissues of mice treated with CR (p < 0.01). Conclusion: In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.

Wedelolactone alleviates hyperoxia-induced acute lung injury by regulating ferroptosis

To study whether wedelolactone can reduce hyperoxia-induced acute lung injury (HALI) by regulating ferroptosis, and provide a basic theoretical basis for the drug treatment of HALI. A total of 24 C57BL/6J mice were randomly divided into normal oxygen control group, HALI model group and wedelolactone pretreatment group, with 8 mice in each group. Mice in wedelolactone pretreatment group were treated with wedelolactone 50 mg/kg intraperitoneally for 6 hours, while the other two groups were not given with wedelolactone. After that, the HALI model was established by maintaining the content of carbon dioxide < 0.5% and oxygen > 90% in the molding chamber for 48 hours, and the normal oxygen control group was placed in indoor air. After modeling, the mice were sacrificed and lung tissues were collected. The lung histopathological changes were observed under light microscope and pathological scores were performed to calculate the ratio of lung wet/dry mass (W/D). The levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in lung tissues of mice in each group were determined. The protein expression of glutathione peroxidase 4 (GPX4) in lung tissue was detected by Western blotting. Under light microscope, the alveolar structure of HALI model group was destroyed, and a large number of neutrophils infiltrated the alveolar and interstitial lung, and the interstitial lung was thickened. The pathological score of lung injury (score: 0.75±0.02 vs. 0.11±0.01) and the ratio of lung W/D (6.23±0.34 vs. 3.68±0.23) were significantly higher than those in the normal oxygen control group (both P < 0.05). Wedelolactone pretreated mice had clear alveolar cavity and lower neutrophil infiltration and interstitial thickness than HALI group. Pathological scores (score: 0.43±0.02 vs. 0.75±0.02) and W/D ratio (4.56±0.12 vs. 6.23±0.34) were significantly lower than HALI group (both P < 0.05). Compared with the normal oxygen control group, the levels of SOD (kU/g: 26.41±4.25 vs. 78.64±3.95) and GSH (mol/g: 4.51±0.33 vs. 12.53±1.25) in HALI group were significantly decreased, while the levels of MDA (mmol/g: 54.23±4.58 vs. 9.65±1.96), TNF-α (μg/L: 96.32±3.67 vs. 11.65±2.03), IL-6 (ng/L: 163.35±5.89 vs. 20.56±3.63) and IL-1β (μg/L: 72.34±4.64 vs. 15.64±2.47) were significantly increased, and the protein expression of GPX4 (GPX4/β-actin: 0.44±0.02 vs. 1.00±0.09) was significantly decreased (all P < 0.05). Compared with the HALI group, the levels of SOD (kU/g: 53.28±3.69 vs. 26.41±4.25) and GSH (mol/g: 6.73±0.97 vs. 12.53±1.25) were significantly higher in the wedelolactone pretreatment group, and the levels of MDA (mmol/g: 25.36±1.98 vs. 54.23±4.58), TNF-α (μg/L: 40.25±4.13 vs. 96.32±3.67), IL-6 (ng/L: 78.32±4.65 vs. 163.35±5.89), and IL-1β (μg/L: 30.65±3.65 vs. 72.34±4.64) were significantly lower (all P < 0.05), and protein expression of GPX4 was significantly higher (GPX4/β-actin: 0.68±0.04 vs. 0.44±0.02, P < 0.05). Wedelolactone attenuates HALI injury by regulating ferroptosis.

Molsidomine decreases hyperoxia-induced lung injury in neonatal rats.

The study's objective is to evaluate if Molsidomine (MOL), an anti-oxidant, anti-inflammatory, and anti-apoptotic drug, is effective in treating hyperoxic lung injury (HLI). The study consisted of four groups of neonatal rats characterized as the Control, Control+MOL, HLI, HLI + MOL groups. Near the end of the study, the lung tissue of the rats were evaluated with respect to apoptosis, histopathological damage, anti-oxidant and oxidant capacity as well as degree of inflammation. Compared to the HLI group, malondialdehyde and total oxidant status levels in lung tissue were notably reduced in the HLI + MOL group. Furthermore, mean superoxide dismutase, glutathione peroxidase, and glutathione activities/levels in lung tissue were significantly higher in the HLI + MOL group as compared to the HLI group. Tumor necrosis factor-α and interleukin-1β elevations associated with hyperoxia were significantly reduced following MOL treatment. Median histopathological damage and mean alveolar macrophage numbers were found to be higher in the HLI and HLI + MOL groups when compared to the Control and Control+MOL groups. Both values were increased in the HLI group when compared to the HLI + MOL group. Our research is the first to demonstrate that bronchopulmonary dysplasia may be prevented through the protective characteristics of MOL, an anti-inflammatory, anti-oxidant, and anti-apoptotic drug. Molsidomine prophylaxis significantly decreased the level of oxidative stress markers. Molsidomine administration restored the activities of antioxidant enzymes. Molsidomine prophylaxis significantly reduced the levels of inflammatory cytokines. Molsidomine may provide a new and promising therapy for BPD in the future. Molsidomine prophylaxis decreased lung damage and macrophage infiltration in the tissue.

Pachymic acid ameliorates bleomycin-induced pulmonary fibrosis through inhibiting endoplasmic reticulum stress in rats.

The effect of pachymic acid (PA) on pulmonary fibrosis in rats was expected to be investigated in this study. Firstly, bleomycin (BLM) was used to establish pulmonary fibrosis rat model, then PA (10, 20, or 40 mg/kg) was intragastrically administered to the rats for 14 days. Subsequently, a variety of tests was performed to observe changes in sample tissues after different treatments. Briefly, the degree of pulmonary edema in rats was assessed through dry/wet weight ratio. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to observe the pathological injury and fibrosis of lung tissue. Biochemical kits were applied to measure the levels of hydroxyproline (Hyp), transforming growth factor beta-1 (TGFβ-1), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) and the activities of superoxide dismutase (SOD) and catalase (CAT) in rat lung tissues of each group. The mitochondrial DNA (mtDNA) copy number in rat lung tissue was tested using qRT-PCR. Additionally, the western blot was employed to detect the expression levels of pulmonary fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in each group of rat lung tissue. By virtue of experimental verification above, PA was discovered to alleviate BLM-induced pulmonary edema, pulmonary fibrosis and histopathological damage. On the one hand, PA treatment decreased Hyp and TGF-β1 levels and down-regulated pulmonary fibrosis-related protein expression [collagen I, α-smooth muscle actin (α-SMA), and fibronectin] in the lung tissue of BLM rats. On the other hand, it significantly increased the levels of SOD, CAT and ATP while decreased the activities of MDA and ROS in BLM rat lung tissues. In addition, the expression levels of ER stress-related proteins [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase 9, and activating transcription factor 4 (ATF4)] were significantly down-regulated in the lung tissue of BLM rats after PA treatment. Collectively, PA may ameliorate BLM-induced pulmonary fibrosis and histopathological damage in rats through inhibiting ER stress and improving mitochondrial function.

P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats.

Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15mg/kg A-438079. The increase in circulatory IL-1β and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL-1β level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats.

MSC-EXO and tempol ameliorate bronchopulmonary dysplasia in newborn rats by activating HIF-1α.

Bronchopulmonary dysplasia (BPD) is a major complication of premature infants and an important cause of morbidity and mortality. This study investigates the effect of the combination of mesenchymal stem cells-derived exosomes (MSC-EXO) and tempol on BPD and analyzes its mechanism. MSC-EXO was extracted by centrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis, and western blot analysis(WB). Tidal volume (TV), minute ventilation (MV), peak inspiratory flow (PIF), and dynamic pulmonary compliance (Cdyn) of rats were measured by BuxCo pulmonary function experimental platform. Hematoxylin-eosin staining was performed to observe the lung morphology and radical alveolar count (RAC)and mean linear intercept (MLI) were assessed. Immunofluorescence (IF) was conducted to detect the expression of CD31 and α-SMA in pulmonary blood vessels. The kits were used to calculate malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAOC) concentration in lung tissue. Enzyme linked immunosorbent assaywas applied to detect the levels of IL-1β, IL-17, IL-6, and IFN-γ in bronchoalveolar lavage fluid. In addition, the expressions of HIF-1α, vascular endothelial growth factor(VEGF), p-PI3K, and p-AKT were analyzed by WB and IF. We successfully extracted and identified MSC-EXO. In BPD rats, TV, MV, PIF, and Cdyn decreased, alveoli were simplified, and the number of interalveoli small vessels, blood vessel density decreased. Moreover, RAC, CD31, TAOC, and SOD decreased, and MLI, α-SMA, MDA, IL-1β, IL-17, IL-6, and IFN-γ increased, which was reversed by the combination of MSC-EXO and tempol treatment after combined treatment. In addition, the expression levels of HIF-1α, VEGF, p-PI3K, and p-AKT were increased after combined treatment. Combined treatment could improve lung tissue injury, promote pulmonary vascular remodeling, restore lung function, and inhibit oxidative stress in BPD rats. These effects were achieved through activation of HIF-1α.

Effects of total ginsenosides from Panax ginseng stems and leaves on gut microbiota and short-chain fatty acids metabolism in acute lung injury mice

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.

Isoegomaketone alleviates inflammatory response and oxidative stress in sepsis lung injury.

Sepsis is a life-threatening condition characterized by acute organ dysfunction, which frequently leads to acute lung injury (ALI) in approximately 40% of cases. Isoegomaketone (IK) is a constituent of essential oil found in P. frutescens, known for its diverse biological properties, including anti-inflammatory and antitumor effects. However, the regulatory impact of IK on ALI in the context of sepsis remains poorly understood. Pathological alterations in lung tissues were assessed using hematoxylin and eosin staining. Enumeration of total leukocytes and neutrophils in bronchoalveolar lavage fluid (BALF) was performed using a hematocytometer, while the levels of interleukin (IL)-6, IL-1β, IL-10, and IL-17 in BALF were quantified using enzyme-linked immunosorbent serological assay. In addition, the levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione (GSH) in lung tissues were assessed using respective commercial kits; cell apoptosis was evaluated using the terminal deoxynucleotide transferase--mediated dUTP nick end-labeling assay, and protein expressions were determined through Western blot analysis. Our findings revealed that cecal ligation and puncture (CLP) treatment in mice induced severe lung injury, characterized by increased lung injury scores, significant bleeding, neutrophil infiltration, and alveolar edema. However, treatment with IK at a dose of 10 mg/kg ameliorated CLP-induced lung injury, while IK dose of 5 mg/kg showed no significant effect. Additionally, IK treatment at 10 mg/kg reduced CLP-induced inflammation by decreasing levels of IL-6, IL-1β, IL-10, and IL-17. Furthermore, IK at 10 mg/kg attenuated CLP-induced oxidative stress by modulating levels of MDA, MPO, SOD, and GSH. Moreover, IK treatment with a dose of 10 mg/kg activated the nuclear factor erythroid 2-related factor 2-heme oxygenase-1 (Nrf2-HO-1) pathway by enhancing the protein expressions of Nrf2 and HO-1. This study demonstrates that IK could mitigate the inflammatory response and oxidative stress associated with sepsis-induced ALI, supporting IK as a promising therapeutic agent for the treatment of sepsis-associated ALI.

Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Effect of Capparis spinosa Fruit Hydroalcoholic Extract on Paraquat-Induced Pulmonary Fibrosis in the Rat.

Pulmonary fibrosis (PF) is a lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. Paraquat is commonly used in agricultural settings to control weed growth and is one of the important risk factors for PF. Additionally, emerging evidence has demonstrated Capparis spinosa (C. spinose) fruit extract has anti-fibrotic, anti-inflammatory, and antioxidant properties. We aimed to evaluate whether C. spinose fruit hydroalcoholic extract has a positive effect against Paraquat-induced PF in rats. 30 male Wistar rats were randomly divided into 5 groups, which included: a control group, a Paraquat control group, a C. spinose group with a dose of 20 mg/kg, a C. spinose group with a dose of 30 mg/kg, a C. spinose group with a dose of 50 mg/kg. After 21 days of the treatment, levels of hydroxyproline and malondialdehyde (MDA) in lung tissue were assessed and lung indices and semi-quantitative histopathological changes were determined. The results showed that treatment with C. spinose, led to increased weight gain, whereas reduced lung weight.C. spinose demonstrated a decreasing effect on levels of MDA, and hydroxyproline in lung tissue. Moreover, histopathological data and the number of lung indices indicated the preventive role of C. spinose Paraquat-induced PF in rats.

The mechanism underlying ICAM-1 and E-selectin-mediated hypertriglyceridemic pancreatitis-associated lung injury

PurposeTo investigate the possible mechanism by which adhesion molecules ICAM-1 and E-selectin mediate hypertriglyceridemic pancreatitis (HTGP)-associated lung injury. MethodsC57BL/6 mice were randomly divided into five groups: control group (Con), severe acute pancreatitis group (SAP), HTGP group (HTGP), A-205804 group (A-205804), and apocynin group (Apo). Serum biochemical markers related to pancreatitis, such as inflammatory cytokines, amylase and lipase, were measured by enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (HE) staining was used to analyze the histopathology changes in the pancreas and lung, and myeloperoxidase (MPO) activity in lung was detected by immunohistochemistry (IHC). Molecules related to NF-κB signaling pathway and adhesion molecules were assessed by western blotting (WB), IHC and immunofluorescence staining. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in lung tissues and serum were measured with reagent kits, respectively. ResultsThe severity of pancreatitis and lung injury in HTGP group was more severe than that in SAP group, and the expression levels of adhesion molecules ICAM-1 and E-selectin in lung tissues of HTGP mice were significantly increased. After HTGP mice were treated with adhesion molecule inhibitor A-205804, the expression of ICAM-1 and E-selectin in A-205804 group significantly decreased, and the lung injury was alleviated. The HTGP group had higher levels of oxidative stress and NF-κB pathway-related protein p-p65 expression compared with the SAP group. Apocynin treatment resulted in suppression of p-p65, ICAM-1, and E-selectin expression. ConclusionIn HTGP, hypertriglyceridemia may exacerbate pancreatitis-related lung injury by regulating oxidative stress and activating the NF-κB proinflammatory pathway to upregulate ICAM-1 and E-selectin levels.

Roles of alpha-7 nicotinic acetylcholine receptors and spleen in the lung injury induced by a repeated saline lavage in rat

BackgroundThe study aimed to determine whether or notα7 nicotinic acetylcholine receptors (α7nAChR) induce anti-inflammatory effects directly in the lung or through the spleen pathway in a sterile model of lung injury by saline lavage.MethodsMale Sprague Dawley rats were divided into seven groups; Sham, splenectomy (SPX), saline lavage (LAV), LAV treated with α7nAChR agonist nicotine (LAV + NIC), and LAV treated with NIC and a selective α7nAChR antagonist MLA (LAV+MLA+NIC), LAV and splenectomy (LAV+SPX), and LAV+SPX treated with nicotine (LAV+SPX+NIC). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. Animals were subjected to volume-controlled ventilation and lung injury by 10 repeated saline lavages. Splenectomy was achieved one week before the induction of lung injury. The recovery phase lasted for 3 h, and drugs were injected 1 h after the last lavage.ResultsMean arterial blood pressure (MBP), heart rate (HR), PaO2, PaO2/FiO2 ratio, and pH decreased, whereas, maximal inspiratory (MIP) and expiratory (MEP) pressures, and PaCO2 increased 1 h after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV + NIC group. MLA or SPX prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV + NIC and LAV + SPX + NIC groups, though it was inhibited by MLA in the LAV + MLA + NIC group. The increases of plasma and lung tissue malondialdehyde (MDA) in the LAV group were diminished by nicotine, whereas, MLA and SPX prevented these reductions. Besides, nicotine could reduce plasma MDA in the LAV + SPX + NIC group. Total BAL cell count, protein BAL/protein plasma ratio, and lung histological scores were attenuated by nicotine in the LAV + NIC group, whereas, MLA reversed the mentioned alterations in the LAV + MLA + NIC group. However, splenectomy could not stop the decreasing effect of nicotine on the total BAL cell in the LAV + SPX + NIC group.ConclusionsIn this study, we indicated that α7nAChR and spleen play roles in cholinergic anti-inflammatory pathways in saline lavage-induced lung injury. However, our results are in favor of at least some direct effects of α 7nAChR in the lung.

Immunomodulatory effect of N-acetyl-seryl-aspartyl-proline and vasoactive intestinal peptide on chronic obstructive pulmonary disease pathophysiology.

Chronic obstructive pulmonary disease (COPD) as an inflammatory respiratory system disease is caused by exposure to cigarette smoke and tobacco in long-term. Some anti-inflammatory peptides can control inflammation in COPD. N-acetyl-seryl-aspartyl-proline (Ac-SDKP) and vasoactive intestinal peptide (VIP) as peptide have anti-inflammatory effect, and, in this study, the effect of Ac-SDKP and VIP on COPD inflammation was studied. After producing cigarette smoke-induced COPD mice model, which were treated with VIP and Ac-SDKP, the levels of antioxidant-related factors (malondialdehyde (MDA) and superoxide dismutase (SOD)), fibrotic factors (hydroxyproline (HP) and TGF-β), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and inflammation in histopathological examination were studied. MDA, Remodeling factors, pro-inflammatory cytokines, and inflammation in lung tissue were controlled by VIP and Ac-SDKP treatment. These treatments could enhance SOD. VIP and Ac-SDKP as immuno-regulatory factors had benefit effect in treatment of COPD. The anti-inflammatory, anti-fibrosis, and anti-oxidant properties of VIP and Ac-SDKP may be effective therapy in COPD.

Effect of Ethyl Acetate Fraction from Eucommia ulmoides Leaves on PM2.5-Induced Inflammation and Cognitive Dysfunction.

This study aimed to evaluate the protective effect of the ethyl acetate from Eucommia ulmoides leaves (EFEL) on PM2.5-induced cognitive impairment in BALB/c mice. EFEL improved PM2.5-induced cognitive decline by improving spontaneous alternative behavioral and long-term memory ability. EFEL increased ferric reducing activity power (FRAP) in serum. In addition, EFEL increased superoxide dismutase (SOD) and reduced glutathione (GSH) contents and inhibited the production of malondialdehyde (MDA) in lung and brain tissues. EFEL also restored the mitochondrial function by regulating reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) level, and ATP level in lung and brain tissues. EFEL ameliorated the cholinergic system by regulating the acetylcholine (ACh) content and acetylcholinesterase (AChE) activity in the brain tissue and the expression of AChE and choline acetyltransferase (ChAT) in the whole brain and hippocampal tissues. EFEL reduced PM2.5-induced excessive expression of inflammatory protein related to the lung, whole brain, olfactory bulb, and hippocampus. Physiological compounds of EFEL were identified as 5-O-caffeolyquinic acid, rutin, quercetin, and quercetin glycosides. As a result, EFEL has anti-inflammation and anti-amnesic effect on PM2.5-induced cognitive impairment by regulating the inflammation and inhibiting the lung and brain tissue dysfunction, and its effect is considered to be due to the physiological compounds of EFEL.

Remifentanil reduces multiple organ and energy metabolism disturbances in a rat sepsis model.

The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil might inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS.

Reducing effects of ginkgo biloba (egb761) extract on skeletal muscle ischemia-reperfusion injury in rats

Aim: The restoration of circulation following a period of ischemia results in the release of the metabolites that accumulate in the ischemic tissue into circulation with untoward effects on the organs. Many studies have been conducted to date into the prevention of such ischemia-reperfusion injuries. Ginkgo Biloba extract is known to have antioxidant effects, although there is a lack of data on its effects on a skeletal muscle ischemia-reperfusion model. The present study investigates the use of Ginkgo biloba extract (egb761) for the reduction of experimentally-induced skeletal muscle ischemia-reperfusion injury. Material and Methods: A total of 32 Sprague-Dawley rats were divided into four groups as follows: Group 1 (n=8), control group; Group 2 (n=8), limb ischemia model; Group 3 (n=8), ischemia-reperfusion model; and Group 4 (n=8), Ginkgo biloba group. After the models were created in each group, soleus muscle, lung and liver tissues were removed. Tissue malondialdehyde (MDA) levels were measured biochemically to demonstrate lipid peroxidation. The percentage of viable cells in the soleus muscle was calculated through a histochemical examination. Results: The comparison of soleus muscle MDA levels revealed no statistically significant difference between Group 1 and Groups 2 and 3, whereas the levels were significantly lower in Group 1 than those in Group 4 (p&lt;0.05). Similarly, there was a significant reduction in Group 4 than in Group 3 (p&lt;0.05). The analysis of lung tissue MDA levels revealed no significant difference between Group 1 and Group 2, whereas MDA levels were significantly increased in Group 3 than in Group 1 (p&lt;0.05), while there was no difference between Group 1 and Group 4. The analysis of liver tissue MDA levels showed significantly increased levels in Groups 3 and 4 than in Group 1 (p&lt;0.05). The percentage of viable cells was significantly decreased in Groups 2 and 3 than in Group 1 (p&lt;0.05). There was a significant reduction in Group 4 than in the control group. Conclusion: The results of the present study suggest that Ginkgo biloba (EGb761) extract may be used to reduce the local and systemic effects occurring after the restoration of blood flow following acute arterial occlusion. There is, however, an apparent need for large-scale, prospective, randomized trials to demonstrate the efficacy of Ginkgo biloba treatment.