Role of SIRT1 signaling pathway in endotoxin-induced acute lung injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of silent information regulator 1 (SIRT1) signaling pathway in endotoxin-induced acute lung injury (ALI) in rats.Methods Ninety-six clean-grade healthy male Sprague-Dawley rats,aged 4 weeks,weighing 160-180 g,were divided into 4 groups (n=24 each) using a random number table method:control group (group C),ALI group,ALI + SIRT1 agonist SRT1720 group (group SRT),and ALI + SIRT1 inhibitor EX527 group (group EX).ALI was induced by injecting lipopolysaccharide (LPS) 5 mg/kg (diluted to 0.5 ml with 0.9％ normal saline) in ALI,SRT and EX groups.SRT1720 10 mg/kg was injected via the tail vein,and 30 min later ALI model was established in group SRT.EX527 1 μg/kg was injected via the tail vein,and 30 min later ALI model was established in group EX.Blood samples were collected from the abdominal aorta at 6,24 and 48 h after LPS injection for blood gas analysis,rats were then sacrificed and lungs were removed for determination of wet to dry weight ratio (W/D ratio) and expression of SIRT1,nuclear factor kappa B p65 (NF-κB p65),interleukin-6 (IL-6) and IL-1β protein and mRNA (by Western blot or real-time polymerase chain reaction) and for examination of pathological changes of lung tissues (with a light microscope).Results Compared with groups C,PaO2 was significantly decreased,and PaCO2 and W/D ratio were increased at each time point after LPS injection in ALI,SRT and EX groups,the expression of SIRT1 protein and mRNA was significantly down-regulated,and the expression of NF-κB p65,IL-6 and IL-1β protein and mRNA was upregulated at each time point after LPS injection in ALI and EX groups,and the expression of SIRT1,NFκB p65,IL-6 and IL-1β was significantly up-regulated at each time point after LPS injection in group SRT (P＜0.05).Compared with group ALI,PaO2 was significantly increased,PaCO2 and W/D ratio were decreased,the expression of SIRT1 protein and mRNA was up-regulated,the expression of NF-κB p65,IL-6 and IL-1β protein and mRNA was down-regulated at each time point after LPS injection (P＜0.05),and the pathological changes were significantly attenuated in group SRT,and no significant change was found in the parameters mentioned above at each time point after LPS injection in group EX (P＞0.05).Conclusion Inhibited SIRT1/NF-κB signaling pathway is involved in endotoxin-induced ALI in rats.