Rat Model Of Sepsis Research Articles

Protective effect of S-nitrosoglutathione pretreatment on acute lung injury in septic rats.

Objective(s):To investigate the protective effect of S-nitrosoglutathione (SNG) pretreatment on acute lung injury (ALI) in septic rats. Materials and Methods:We constructed a rat model of sepsis by cecal ligation and perforation (CLP), and randomly divided into Sham, CLP, and CLP+SNG (0.25 and 0.5 mg/kg) groups. We used H&E staining and lung wet/dry ratio to assess the severity of lung injury, detected the levels of protein and cells in bronchoalveolar lavage fluid (BALF) and the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA in the lung tissue, and assessed the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in the lung tissue.Results:A rat model of sepsis was successfully constructed by CLP, and pretreatment of SNG significantly increased the survival of septic rats (P<0.001) and decreased the lung tissue injury scores (P<0.001) and lung wet/dry ratio (P<0.01) in a dose-dependent manner. Furtherly, SNG pretreatment significantly reduced the number of total cells, total protein, neutrophils, and lympholytes (all P<0.001) in BALF, and which also decreased the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA (all P<0.001) in the lungs of CLP-induced rats. Moreover, pretreatment of SNG significantly increased the levels of anti-oxidant enzymes GSH, SOD, GSH-Px, and catalase (all P<0.001) in the lung tissue of septic rats. Conclusion:SNG pretreatment has a protective effect on ALI in septic rats, and the specific mechanism may be related to anti-endotoxic, anti-inflammatory, and anti-oxidative properties.

Effects of Lacosamide in Rats with Lipopolysaccharide Induced Hepatic Pathology

Bacterial lipopolysaccharides (LPS) generally increase the pathogenicity of the agent. This study aimed to examine the hepatic pathology and possible prophylactic effects of lacosamide (LCM) in a LPS-induced sepsis rat model. Overall, 24 1-year-old female Wistar Albino rats were divided into three groups: Group I (control), Group II (LPS group: 5 mg/kg LPS intraperitoneally, single dose), and Group III (LCM group: 40 mg/kg LCM intraperitoneally once daily for 3 days plus 5 mg/kg LPS 30 min after the last LCM treatment). Animals were euthanized 6 hours after LPS administration. Blood and liver samples collected during necropsy were analyzed biochemically, pathologically, and immunohistochemically. LPS caused a significant increase in serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, and alkaline phosphatase levels. Histopathological analysis revealed numerous neutrophil leucocyte infiltrations, slight hemorrhages in the liver, and degenerative or necrotic changes in hepatocytes. Increased expressions of malondialdehyde, C-reactive protein, heat shock protein-70, interleukin-1β, and tumor necrosis factor-α were observed in the LPS administered group. LCM ameliorated the biochemical, histopathological, and immunohistochemical findings. The present study results revealed that LCM ameliorated the LPS-induced liver damage in the rat models as evidenced by the biochemical and pathological findings.

Therapeutic Effect of Statins and LPS Antibody on Proinflammatory Mediator and Biochemical Markers of Sepsis Rat Model Induced by E. coli

This study aims to determine the effect of statins and LPS antibodies administration combined with E. coli intraperitoneal injection toward proinflammatory mediators (TNF-?, hs-CRP, PCT, and MDA) urea, BUN, and creatinine) and liver function (SGPT, SGOT, and total bilirubin) in sepsis rats. This study used 30 male white rats (Rattus novergicus strain Wistar) divided into 6 groups induced by E. coli bacteria combined with statins, LPS antibody (Ab-LPS), and a combination of statins+Ab-LPS. Examination of proinflammatory mediators (TNF-?, hs-CRP, PCT, and MDA) was carried out by the ELISA method through the examination of biochemical markers namely renal function (urea, BUN, and creatinine) and liver function (SGPT, SGOT, and total bilirubin) were analyzed by using the autoanalyzer. The data obtained were statistically analyzed using the T-test. The result shows that E. coli+statins gave significant changes on the MDA level at 0th hour administration and TNF-? and hs-CRP at 3rd hour administration. The E. coli+Ab-LPS treatment showed significant changes at the 0th hour administration for MDA, creatinine, and total bilirubin and at the 3rd hour administration for MDA. The E. coli+statins+Ab-LPS treatment showed significant changes in MDA, creatinine, and total bilirubin at 0th hour administration and on creatinine and total bilirubin at 3rd hour administration.

Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages

BackgroundDespite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis.MethodshAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis.ResultsProphylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways.ConclusionsProphylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

Immunomodulator effect of ketamine on rat models of sepsis (fecal induced peritonitis): Eosinophil and monocyte modulation

Sepsis is a result of dysregulated inflammation and it affects the inflammatory mediator cell production. Ketamine has an immunomodulatory effect and it can be used in the sepsis immunotherapy. We conducted this study to determine the effect of ketamine on the number of eosinophils and monocytes in the rat model of sepsis.

2-Chlorofatty acids are biomarkers of sepsis mortality and mediators of barrier dysfunction in rats

Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitro endothelial barrier function, and activate human neutrophil extracellular trap formation. Here, we sought to examine 2-CLFAs in an in vivo rat sepsis model. Intraperitoneal cecal slurry sepsis with clinically relevant rescue therapies led to ∼73% mortality and evidence of microcirculatory dysfunction. Plasma concentrations of 2-CLFAs assessed 8 h after sepsis induction were lower in rats that survived sepsis than in nonsurvivors. 2-CLFA levels were elevated in kidney, liver, spleen, lung, colon, and ileum in septic animals. In vivo, exogenous 2-CLFA treatments increased kidney permeability, and in in vitro experiments, 2-CLFA also increased epithelial surface expression of vascular cell adhesion molecule 1 and decreased epithelial barrier function. Collectively, these studies support a role of free 2-CLFAs as biomarkers of sepsis mortality, potentially mediated, in part, by 2-CLFA-elicited endothelial and epithelial barrier dysfunction.

NLRP3 inflammasome inhibition attenuates sepsis-induced platelet activation and prevents multi-organ injury in cecal-ligation puncture.

Sepsis is characterized by organ dysfunction due to a dysregulated immune response to infection. Currently, no effective treatment for sepsis exists. Platelets are recognized as mediators of the immune response and may be a potential therapeutic target for the treatment of sepsis. We previously demonstrated that NLRP3 inflammasome activation in sepsis-induced activated platelets was associated with multi-organ injury in the cecal-ligation puncture (CLP) rat model of sepsis. In this study, we tested the hypothesis that inhibition of NLRP3 would inhibit platelet activation and attenuate multi-organ injury in the CLP rat. CLP (n = 10) or Sham (n = 10) surgery were performed in male and female Sprague-Dawley rats. A subset of CLP rats were treated with MCC950 (50mg/kg/d), a specific NLRP3 inhibitor (CLP+MCC950, n = 10). At 72 hrs. post-CLP, blood and organs were harvested for analysis of platelet activation, NLRP3 activation, inflammation and end organ damage. Platelet activation increased from 8±0.8% in Sham to 16±1% in CLP, and was reduced to 9±1% in CLP+M rats (p<0.05). NLRP3 activation was also increased in platelets of CLP vs Sham. NLRP3 expression was unchanged in kidney and lung after CLP, but Caspase 1 expression and IL-1β were increased. MCC950 treatment attenuated NLRP3 activation in platelets. Plasma, kidney, and lung levels of NLRP3 inflammasome associated cytokines, IL-1ß and IL-18, were significantly increased in CLP compared to Sham rats. Inhibition of NLRP3 normalized cytokine levels. Glomerular injury, pulmonary edema, and endothelial dysfunction markers were increased in CLP rats vs Sham. MCC950 treatment significantly decreased renal and pulmonary injury and endothelial dysfunction in CLP+M. Our results demonstrate a role for NLRP3 in contributing to platelet activation and multi-organ injury in sepsis.

Hypertonic sodium lactate improves microcirculation, cardiac function, and inflammation in a rat model of sepsis

BackgroundHypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)).MethodsThree groups were analyzed (n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics (n = 7/group).ResultsHSL improved mesenteric microcirculation (CLP-HSL 736 [407–879] vs. CLP-NaCl 241 [209–391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28–0.43] vs. 0.14 [0.10–0.18] mL/min/g, p < 0.0001), and left ventricular fractional shortening (55 [46–73] vs. 39 [33–52] %, p = 0.009). HSL also raised dP/dtmax slope (6.3 [3.3–12.1] vs. 2.7 [2.0–3.9] 103 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1–2.3] vs. 3.0 [2.2–3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31–43] vs. 113 [63–142], p = 0.03), the lung (108 [82–174] vs. 273 [222–445], p = 0.006), and the liver (24 [14–37] vs. 70 [50–89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08–10.30] vs. 3.19 [2.42–5.11] mmol/L, p = 0.04; 400 [174–626] vs. 189 [130–301] μmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1β, 172 [119–446] vs. 928 [245–1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5–50.3] vs. 53.9 [30.8–85.6] pg/mL, p = 0.005; IL-10, 352 [267–912] vs. 905 [723–1243] pg/mL) as well as plasma VEGF-A (198 [185–250] vs. 261 [250–269] pg/mL, p = 0.009).ConclusionsHypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.

Flufenamic acid alleviates sepsis-induced lung injury by up-regulating CBR1.

Investigate the effect of flufenamic acid (FFA) on lung injury of sepsis rats. Rat sepsis model was established using cecal ligation and puncture (CLP). The pathomorphology of lung tissue was detected by Hematoxylin-eosin (H&E) staining. The expression levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and high mobility group box-1 (HMGB-1) in serum and TNF-α, IL-6, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in lung tissues. The viability of RLE-6TN cells was detected by CCK-8 assay. The expression of carbonyl reductase 1 (CBR1) in RLE-6TN cells was analyzed by Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The inflammatory response was obviously enhanced in CLP-constructed sepsis rats and alleviated by FFA treatment. Sepsis induced the increase of W/D ratio, promoted the levels of TNF-α, IL-6, HMGBR1, and MDA and inhibited the levels of SOD and GSH. FFA could effectively alleviate the sepsis-induced lung injury. The viability of RLE-6TN cells induced by LPS was improved with the treatment of FFA. CBR1 expression in LPS-induced RLE-6TN cells was decreased and FFA could up-regulate the CBR1 expression. In addition, LPS-induced lung injury promoted the inflammatory response in lung tissues, increased the W/D ratio and levels of TNF-α, IL-6, HMGBR1, and MDA while inhibited the levels of SOD and GSH. FFA could effectively improve the LPS-induced lung injury while the effect of FFA on LPS-induced lung injury was alleviated by CBR1 interference. FFA may alleviate sepsis-induced lung injury by up-regulating CBR1.

Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial

BackgroundEndotoxins can induce an excessive inflammatory response and result in microcirculatory dysfunction. Polymyxin-B hemoperfusion (PMX-HP) has been recognized to effectively remove endotoxins in patients with sepsis and septic shock, and a rat sepsis model revealed that PMX-HP treatment can maintain a better microcirculation. The primary aim of this study was to investigate the effect of PMX-HP on microcirculation in patients with septic shock.MethodsPatients with septic shock were enrolled and randomized to control and PMX-HP groups. In the PMX-HP group, patients received the first session of PMX-HP in addition to conventional septic shock management within 24 h after the onset of septic shock; the second session of PMX-HP was provided after another 24 h as needed.ResultsOverall, 28 patients finished the trial and were analyzed. The mean arterial pressure and norepinephrine infusion dose did not differ significantly between the control and PMX-HP groups after PMX-HP treatment. At 48 h after enrollment, total vessel density (TVD) and perfused vessel density (PVD) were higher in the PMX-HP group than in the control group [TVD 24.2 (22.1–24.9) vs. 21.1 (19.9–22.9) mm/mm2; p = 0.007; PVD 22.9 (20.9–24.9) vs. 20.0 (18.9–21.6) mm/mm2, p = 0.008].ConclusionsThis preliminary study observed that PMX-HP treatment improved microcirculation but not clinical outcomes in patients with septic shock at a low risk of mortality. Nevertheless, larger multicenter trials are needed to confirm the effect of PMX-HP treatment on microcirculation in patients with septic shock at intermediate- and high-risk of mortality.Trial registration ClinicalTrials.gov protocol registration ID: NCT01756755. Date of registration: December 27, 2012. First enrollment: October 6, 2013. https://clinicaltrials.gov/ct2/show/NCT01756755

Mechanism of Systemic Inflammatory Regulation in Sepsis Rat Models Through the Role of HMGB1, IL-1?, IL-10 and Procalcitonin in Statin Administration

Mechanism of Systemic Inflammatory Regulation in Sepsis Rat Models Through the Role of HMGB1, IL-1?, IL-10 and Procalcitonin in Statin Administration

Mechanism of Systemic Inflammatory Regulation in Sepsis Rat Models Through the Role of HMGB1, IL-1?, IL-10 and Procalcitonin in Statin Administration

Mechanism of Systemic Inflammatory Regulation in Sepsis Rat Models Through the Role of HMGB1, IL-1?, IL-10 and Procalcitonin in Statin Administration

Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation, and survival, in a model of polymicrobial sepsis in rats. Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 h) (group III), and CLP + FMT at 6 h (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6, and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for 7 days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats. HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV: 617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas these increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1.6 ± 0.5, Group II: 5.8 ± 2.4, Group III: 3.6 ± 0.9, Group IV: 2.3 ± 0.6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in tight junction by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/mL, mean ± SD: Group I: 0.93 ± 0.36, Group II: 2.14 ± 1.74, Group III: 1.48 ± 0.53, Group IV: 1.61 ± 0.58), while FMT additionally decreased IL-6 and IL-10 levels. Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.

NMR-based metabolomics approach reveals effects of antioxidant nutrients in sepsis-induced changes in rat liver injury

Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of sepsis. In excess, oxidative stress is not deemed an unbalanced biochemical reaction in the critically ill rats, but it is a key pathological factor in driving systemic inflammatory response that can result in multiple organ failure in sepsis. Thus, we aimed to explore whether antioxidant nutrients could reduce or delay the oxidative stress condition of sepsis rats, and then play a prospective role in the oxidative stress condition of critical disease. In this investigation, the ability of exogenous and endogenous antioxidant nutrients (ascorbate, taurine and glutathione) to prevent sepsis-induced changes in liver injury was examined using a rat model of sepsis induced by cecal ligation and puncture (CLP), and the underlying mechanisms were also investigated. The effects of three antioxidants on sepsis were assessed based on biochemical assays in combination with an NMR-based metabolomics approach and correlation network analysis. Our results suggested that ascorbate, taurine and glutathione had broadly similar protective effects on reducing oxidative stress. Compared with CLP rats, antioxidant-treated rats exhibited alleviated (P<.05) organ dysfunction and improved liver pathology. Moreover, taurine showed a better efficacy compared with ascorbate and glutathione, evidenced by significantly reversed metabolomics profiles toward normal state. Under conditions of sepsis, antioxidants suppressed inflammatory responses by restraining key signaling pathways, including the redox-sensitive transcription factor pathways of NF-κB and MAPK. Collectively, our findings suggested that antioxidant nutrients exerted beneficial effects on septic rats via protecting mitochondrial.

Effects of different crystalloid fluids resuscitation on renal structure and function in sepsis rats

To evaluate the effects of resuscitation with normal saline and sodium potassium magnesium calcium and glucose injection on renal structure and function in septic rats. Rat model of sepsis was established by ligation and perforation of cecum. Male SD rats were divided into four groups: sham operation group, sepsis group, saline resuscitation group, sodium potassium magnesium calcium and glucose injection resuscitation group. Blood gas analysis was performed at the end of resuscitation. The rats were sacrificed 72 hours after resuscitation. Blood samples were taken to measure the plasma levels of blood urea nitrogen (BUN), creatinine, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factorα (TNFα). Caspase-3 expression was detected by immunohistochemistry in kidney sections. The degree of renal injury was evaluated by regular HE staining and electron microscope. Compared with normal saline resuscitation, sodium potassium calcium magnesium glucose injection resuscitation could decrease the levels of BUN, serum creatinine, IL-1β, IL-6 and TNFα (P<0.05) , reduce the expression of caspase-3 (P<0.05) , and improve the renal injury score (P<0.05) . Sodium potassium calcium magnesium glucose injection resuscitation can significantly improve the renal function of sepsis rats with less pathological damage of the kidney.

The activation of IL-17 signaling pathway promotes pyroptosis in pneumonia-induced sepsis

BackgroundPyroptosis is closely relevant to sepsis. However, the molecular mechanisms of pyroptosis in pneumonia-induced sepsis are still not fully understood. Thus, this study aimed to find the specific molecular pathways associated with pyroptosis and explore their relationship in pneumonia-induced sepsis.MethodsFirst, significant signaling pathways related to pneumonia-induced sepsis were screened by bioinformatics analysis based on GSE48080. The peripheral blood samples from patients with pneumonia-induced sepsis and healthy subjects were collected. Pneumonia-induced sepsis rat models were also established. Then, inflammatory response, pyroptosis, and regulatory T cells (Tregs)/T-helper 17 (Th17), Th1/Th2, and M1/M2 cell ratios in pneumonia-induced sepsis were evaluated.ResultsIL-17 signaling pathway was significantly related to pneumonia-induced sepsis by bioinformatics analysis. Compared with healthy groups, the higher of Th17/Treg, Th1/Th2 and M1/M2 cell radios in the patients and sepsis rat model indicated that pneumonia-induced sepsis caused a severe inflammatory response. This result was confirmed by higher levels of pro-inflammatory factors (IL-6, TNF-α, IL-1β, and IL-18) and an inflammation indicator (LDH), as well as pyroptosis occurrence in sepsis. Additionally, the up-regulation of key molecules (HMGB1, RAGE, IL-17A, TRAF6 and NK-κB) in the IL-17 signaling pathway suggested the IL-17 pathway was activated. Moreover, the release of IL-1β and IL-18 and the levels of the molecules (NLRP3, NLRC4, Cleaved caspase-1, and Cleaved GSDMD) associated with caspase-1-dependent pyroptosis were up-regulated in pneumonia-induced sepsis.ConclusionsAs NK-κB activation can promote the development of caspase-1-dependent pyroptosis, these findings suggested that the activation of the IL-17 signaling pathway could promote pyroptosis in pneumonia-induced sepsis.

Cholinergic anti-inflammatory pathway plays negative regulatory role in early inflammatory and immune responses in septic rats

To investigate the role of cholinergic anti-inflammatory pathway (CAP) in neuro-regulation of inflammatory and immune response in the early stage of sepsis. Sixty-four SD rats were randomly divided into control Group (n=8) with normal feeding without any treatment; sham operation group (n=8) with laparotomy but without cecal ligation and puncture (CLP), followed by intraperitoneal injection 50 mg/kg piperacillin 3 times a day for 3 consecutive days; and sepsis group (n=48) with CLP-induced sepsis. The rat models of sepsis were randomized into model groups (n=16) with intraperitoneal injection of piperacillin (50 mg/kg) and normal saline (1 mL/100 g) for 3 times a day for 3 days; GTS-21 group (n=16) with additional intraperitoneal injection of 4 mg/kg GTS-21 (once a day for 3 days); and methyllycaconitine (MLA) group (n=16) with intraperitoneal injection of MLA (4.8 mg/kg) in addition to piperacillin (once a day for 3 days). Murine Sepsis Score (MSS) of the rats and short-range HRV analysis were recorded. Three days later, the rats were sacrificed and serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 were measured with ELISA. The percentages of CD4+CD25+ Treg and TH17 lymphocytes and their ratios were measured using flow cytometry. Compared with the control rats, the septic rats had significantly increased MSS scores and lowered HRV indexes (SDNN, RMSSD, HF, SD1, and SD2; P &lt; 0.05); treatment with GTS-21 significantly decreased while MLA increased MSS scores (P &lt; 0.05), but neither of them obviously affected HRV of the rats. Serum levels TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4+CD25+ Treg and TH17-positive lymphocytes were significantly higher and Treg/TH17 ratio was significantly lower in the septic rats compared with those in the control group (P &lt; 0.05); treatment with GTS-21 significantly decreased the levels of serum levels of TNF-α, IL-1α, IL-6, HMGB1, and sCD14 and TH17 lymphocyte percentage (P &lt; 0.05), whereas MLA treatment significantly increased serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4+ CD25+ Treg and TH17-positive lymphocytes and decreased Treg/TH17 ratio in the septic rats (P &lt; 0.05). CAP plays negative regulatory role in early inflammatory and immune response to sepsis, and some of the HRV indicators can well reflect the regulatory effect of CAP on inflammation and immunity in the septic rats.

RETRACTED: Protective role of long noncoding RNA CRNDE in myocardial tissues from injury caused by sepsis through the microRNA-29a/SIRT1 axis

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editor-in-Chief and the corresponding author. The corresponding author confessed that the paper was outsourced to a third-party company, who could not guarantee the integrity of the data.

Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis.

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)‐induced rat sepsis model. High‐throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real‐time quantitative polymerase chain reaction (RT‐qPCR). Bioinformatic analysis was carried out and coding and non‐coding co‐expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up‐regulated and 428 down‐regulated circRNAs and 2063 up‐regulated and 2903 down‐regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down‐regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.

EFFECT OF PNEUMOPERITONEUM IN MODEL OF ABDOMINAL SEPSIS

ABSTRACT&#x0D; Purpose: This study aims to examine the effects of CO2 pneumoperitoneum on the level of inflammation biomarkers in a model of abdominal sepsis in rats. Methods: Twelve Wistar rats were randomly assigned to two groups of 6 rats each. Under anesthesia, abdominal sepsis was induced by cecal ligation and puncture (CLP). Rats were observed for 24 hours. Group 1: sepsis; group 2: sepsis + pneumoperitoneum with CO2 for 30 min. Six hours after pneumoperitoneum deflation, blood samples were collected by cardiac puncture to measure (TNFα), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (PCR) and procalcitonin (PCT). Statistical analysis using Student t test (p&lt;0.05). Results: All animals survived. The rats with sepsis + pneumoperitoneum had levels of TNFα, IL-1β and IL-6 (542.4 ± 21pg / mL; 312.1 ± 12 pg / mL and 115.4 ± 11 pg / mL (respectively ), significantly lower than in the sepsis group (p = 0.01). Serum cytokine levels in the sepsis group were TNFα = 733.2 ± 24pg / mL; IL-1β = 432.1 ± 15 pg / mL and IL-6 = 232.3 ± 16 pg / mL. Serum levels of PCT and CRP were significantly lower in the sepsis + pneumoperitoneum group than in the sepsis group. (p=0.01). Conclusion: In conclusion, pneumoperitoneum CO2 attenuates the biomarkers of the acute phase inflammatory response associated with perioperative sepsis by PLC.