Acute Lung Injury In Septic Mice Research Articles

Memantine Alleviates Acute Lung Injury Via Inhibiting Macrophage Pyroptosis.

Acute lung injury (ALI) is caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis and trauma. Alveolar macrophages are the main and critical leukocytes in the airspace, and through the synthesis and release of various inflammatory mediators critically influence the development of ALI following infection and non-infectious stimuli. There is increasing recognition that inflammation and cell death reciprocally affect each other, which forms an auto-amplification loop of these two factors, and in turn, exaggerates inflammation. Therefore, pharmacological manipulation of alveolar macrophage death signals may serve as a logical therapeutic strategy for ALI. In this study, we demonstrate that memantine, a N-methyl-D-aspartic acid receptor (NMDAR) antagonist, through suppressing Ca2+ influx and subsequent ASC oligomerization inhibits macrophage Nlrp3 inflammasome activation and pyroptosis, therefore, alleviates ALI in septic mice. This finding explores a novel application of memantine, an FDA already approved medication, in the treatment of ALI, which is currently lacking effective therapy.

Itraq-Based Quantitative Proteomic Analysis of Lungs in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment.

Sepsis-associated acute lung injury (ALI), which carries a high morbidity and mortality in patients, has no effective therapeutic strategies to date. Our group has already reported that hydrogen gas (H2) exerts a protective effect against sepsis in mice. However, the molecular mechanisms underlying H2 treatment are not fully understood. This study investigated the effects of H2 on lung injuries in septic mice through the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis. Male ICR mice used in this study were subjected to cecal ligation and puncture (CLP) or sham operation. And 2% H2 was inhaled for 1 h beginning at 1 and 6 h after sham or CLP operation. The iTRAQ-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was preformed to investigate lung proteomics. Sepsis-challenged animals had decreased survival rate, as well as had increased bacterial burden in blood, peritoneal lavage, and lung sample, which were significantly ameliorated by H2 treatment. Moreover, a total of 4,472 proteins were quantified, and 192 differentially expressed proteins were related to the protective mechanism of H2 against sepsis. Functional enrichment analysis showed that H2-related differential proteins could be related to muscle contraction, oxygen transport, protein synthesis, collagen barrier membranes, cell adhesion, and coagulation function. These proteins were significantly enriched in four signaling pathways, and two of which are associated with coagulation. In addition, H2 alleviates ALI in septic mice through downregulating the expression of Sema 7A, OTULIN, and MAP3K1 as well as upregulating the expression of Transferrin. Thus, our findings provide an insight into the mechanism of H2 treatment in sepsis by proteomic approach, which may be helpful to the clinic application of H2 in patients with sepsis.

Effect of sofren injection on acute lung injury in septic mice

Objective To evaluate the effect of sofren injection on acute lung injury(ALI)in septic mice. Methods Ninety-six pathogen-free male Kunming mice, aged 8-10 weeks, weighing 30-35 g, were divided into 4 groups(n=24 each)using a random number table: sham operation group(group Sham), ALI group, vehicle group(group Vehicle)and sofren injection group(group Sofren). Sepsis was induced by cecal ligation and puncture.In Vehicle and Sofren groups, double distilled water and sofren injection 4 ml/kg were intraperitoneally injected, respectively, after the model was established, followed by repeated administration once every 12 h. At 12, 24 and 48 h after operation, the animals were sacrificed and lungs were removed for microscopic examination and for determination of wet to dry weight ratio(W/D ratio), malondialdehyde(MDA)content, superoxide dismutase(SOD)activity, and contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in lung tissues(by enzyme-linked immunosorbent assay). The lung injury score(LIS)was calculated after haematoxylin and eosin staining. Results Compared with group Sham, the LIS, W/D ratio and contents of MDA, TNF-α and IL-6 were significantly increased, and the SOD activity was decreased at each time point in ALI and Vehicle groups(P 0.05). Conclusion Sofren injection can attenuate ALI in septic mice. Key words: RHODIOLA SACRA; Sepsis; Respiratory distress syndrome, adult