Mouse Model Of Obstructive Pulmonary Disease Research Articles

A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.

Inhibitory Effects of <italic>Ssanghwa-tang</italic> on Lung Injury and Muscle Loss in a Cigarette Smoke Extract and Lipopolysaccharide-induced Chronic Obstructive Pulmonary Disease Mouse Model

Objectives: This study evaluated the effects of <i>Ssanghwa-tang</i> (SHT) on lung injury and muscle loss in a COPD mouse model.Methods: C57BL/6 mice were challenged with cigarette smoke extract and lipopolysaccharide, and then treated with two concentrations of SHT (250 and 500 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed by cytospin, ELISA, real-time PCR, flow cytometry analysis, and H&E and Masson’s trichrome staining. The grip strength of COPD mice was measured using a grip strength meter. The running time of COPD mice was measured by a treadmill test. Muscle tissue of the quadriceps was stained with H&E and Masson’s trichrome staining.Results: SHT significantly inhibited the increase in neutrophil numbers in BALF and significantly decreased immune cell activity in BALF and lung tissue. It also significantly inhibited the increase in TNF-α, IL-17, and MIP2 in BALF. Real-time PCR analysis revealed that the mRNA expression of TNF-α, IL-17, MIP2, and TRPV1 in lung tissue showed a significant decrease compared with the control group. Lung tissue damage was significantly reduced in the histological analysis. The grip strength and running time of the COPD mice showed a significant decrease compared with the control group. In histological staining, SHT was found to reduce the damage to muscle tissue.Conclusions: This study indicates that SHT can be used as a therapeutic agent for COPD patients by inhibiting lung injury and muscle loss.

Anti-inflammatory effect of Gyeji-tang in a chronic obstructive pulmonary disease mouse model induced by cigarette smoke and lipopolysaccharide

Context Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with respiratory symptoms and narrowing of airways. Gyeji-tang (GJT) is a traditional Asian medicine that has been used to relieve early-stage cold symptoms, headache, and chills. Objective We examined the effect and potential molecular action mechanism of GJT in a mouse model of COPD induced by cigarette smoke (CS) plus lipopolysaccharide (LPS). Materials and methods COPD was induced in C57BL/6J mice via daily exposure to CS for 1 h for 8 weeks and intranasal administration of LPS on weeks 1, 3, 5, and 7. GJT (100 or 200 mg/kg) or roflumilast (5 mg/kg) was administrated daily for the final 4 weeks of COPD induction. Results Administration of GJT significantly suppressed the CS/LPS-induced increases in: the numbers of total cells and macrophages in bronchoalveolar lavage fluid; the expression levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1β, and IL-8; the activities (phosphorylation) of nuclear factor kappa B and signal transducer and activator of transcription 3; and the expression levels of the structural remodelling markers, transforming growth factor beta, matrix metallopeptidase (MMP)-7, and MMP-9. Discussion and conclusions These results demonstrate that GJT prevents the lung inflammation and airway remodelling induced by CS plus LPS exposure in mice, suggesting that GJT may have therapeutic potential for the treatment of COPD.

Proteomic analysis of a chronic obstructive pulmonary disease mouse model to determine the efficacy of treatment using Guben Zhike decoction

Guben Zhike decoction (GBZKD) is derived from the experience of Professor Enxiang Chao, an esteemed master of Chinese medicine, while treating chronic obstructive pulmonary disease (COPD). GBZKD reinforces the healthy qi and consolidates defensive qi. This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics. A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration. The model was verified through lung function test and lung histopathological observation. Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD, COPD, and control groups. GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model. Proteomic analysis identified 4316 proteins, of which 3696 were quantitative proteins. We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice, respectively. These proteins participated in multiple functions, including complement/coagulation cascade, immune response, and metabolic pathways. GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.

Effects of GHX02 on Chronic Obstructive Pulmonary Disease Mouse Model

Effects of GHX02 on Chronic Obstructive Pulmonary Disease Mouse Model

Establishment of a chronic obstructive pulmonary disease mouse model based on the elapsed time after LPS intranasal instillation

Chronic obstructive pulmonary disease (COPD) was the 3rd leading cause of death in 2012 worldwide. It is particularly severe in the elderly, who are at risk of death by coughing, mucous hypersecretion, and finally breathlessness. Recently, anti-COPD drug development has increased, and many animal screening systems have been studied. Tobacco smoke animal models are the best known animal screening system, but have several preparation requirements, such as a tobacco smoke generator and a separate facility to prevent smoke release. Accordingly, we evaluated the properties of a lipopolysaccharide (LPS) murine model for COPD screening and the effect of the time elapsed from 0 to 72 hr after LPS intranasal instillation on various biomarkers of COPD severity, such as WBC and neutrophils in bronchoalveolar fluid (BALF), IgE in serum, histopathology in the lung, and cytokines (IL-8, TNF-α, IFN-γ, and TGF-β) and chemokines (CCL-2, CXCL1, CXCL9, CXCL10, and CXCL11) in the respiratory system. Although from 48 hr after LPS treatment several factors which could be evaluated as biomarkers for COPD establishment such as WBC and neutrophil in BALF, IgE in serum, cytokines (IL-8, TNF-α, and IFN-γ), and chemokines (CCL-2, CXCL1, CXCL9, CXCL10, and CXCL11) increased at 72 hr the increment of important factors for COPD establishment such as IgE, fibrosis in the lung, and cytokines (IL-8, TNF-α, and IFN-γ) was more clear. Based on our results, we concluded that the optimal time after LPS intranasal instillation is 72 hr.

Angiotensin-(1-7)-mediated Mas1 receptor/NF-κB-p65 signaling is involved in a cigarette smoke-induced chronic obstructive pulmonary disease mouse model.

Angiotensin-(1-7) [Ang-(1-7)] has been shown to play a significant role in the pathogenesis of lung inflammation via Mas receptor; however, its effect in chronic obstructive pulmonary disease (COPD) remains unknown. To explore the effect of Ang-(1-7) on a cigarette smoke (CS) exposure-induced COPD model, 40 C57BL/6J mice were divided into four groups (n = 10) and exposed to air or CS for 8 weeks. After that, they were treated with saline or Ang-(1-7) at 0.3 mg/kg for 2 weeks by subcutaneous infusion using osmotic pump. The day following drug/vehicle challenge, lung function was examined and bronchoalveolar lavage (BAL) was performed. Chemokine (C-X-C motif) ligand 1, interleukin-6, and tumor necrosis factor-α protein levels in BAL fluid were determined using ELISA; the corresponding mRNA levels in lung tissues were measured using RT-PCR. Mas1 receptor, pIκBα, IκBα, nuclear NF-κB-p65 protein, pERK1/2, ERK2, pp38, and p38 proteins expression in lung tissues were examined by immunohistochemical staining and western blotting. Ang-(1-7) challenge had no effect on the decreased lung function and emphysema induced by CS exposure. However, Ang-(1-7) treatment blocked CS exposure-induced lung inflammatory responses and lung fibrosis, as determined by Masson's Trichrome staining. Exposure to CS for 8 weeks caused irreversible loss of lung function and emphysema, which could not be reversed by Ang-(1-7) treatment. Thus, the beneficial effect of Ang-(1-7) may be confined to pulmonary inflammation and fibrosis.

Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model

Ethnopharmacological relevanceThe tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD Materials and methodsThe ethanol extract of the tuber of A. orientale Juzepzuk (EEAO) was fingerprinted by HPLC. For the establishment of COPD lung, mice received single intratracheal (i.t.) spraying of elastase and LPS per week for 2 weeks. After approximated to the dose prescribed typically to patients, EEAO was administered to the lung 2h after each LPS treatment. Morphometric analyses, semi-quantitative RT-PCR, and western blot were performed to evaluate the effects of EEAO on emphysema, inflammation, and autophagy in mouse lungs. The effect of EEAO on autophagy was also assessed by western blot at the cellular level with murine macrophages and human lung epithelial cells. ResultsWhen receiving i.t. elastase and LPS for 2 weeks, mice developed emphysema and inflammation in the lung. EEAO treatment, however, significantly reduced emphysema and inflammatory cell infiltration to the lung with concomitant decrease of the production of pro-inflammatory cytokines including TNF-α, IL-6, and TGF-β, signature cytokines of COPD. Unlike control mice, the lungs of the COPD mice expressed LC3-II, a biomarker for autophagy formation, which was decreased by EEAO treatment. EEAO also lowered the expression of LC3-II in murine macrophage, RAW 264.7, and human lung epithelial cell, BEAS-2B, which was associated with EEAO activating mTOR. ConclusionEEAO relieved COPD pathologic features in a mouse model, which was associated with suppression of lung inflammation, emphysema, and autophagy. Our results suggest an effectiveness of the tuber of A. orientale in chronic inflammatory lung diseases such as COPD.

Scientific Evidence for Korean Medicine and Its Integrative Medical Research

Scientific Evidence for Korean Medicine and Its Integrative Medical Research