Role of SIRT1 in intestinal ischemia-reperfusion injury in rats

Abstract:

Objective：To investigate the role of SIRT1 in intestinal ischemia-reperfusion injury in rats. Methods：45 rats were divided into sham-operated group，model group and SIRT1 group. The sham-operated group and model group were intraperitoneally injected with adeno-associated virus of empty vector and the SIRT1 group was intraperitoneally injected with adeno-associated virus of over－expression SIRT1. After 21 days of injection，rats in model group and SIRT1 group were treated with superior mesenteric artery oc－clusion-relaxation occlusion to establish small intestinal ischemia-reperfusion model，while rats in sham-operated group were only treated with superior mesenteric artery separation. 24 hours after reperfusion，rats were killed. Serum and small intestine samples were collected. The levels of inflammatory factors of interleukin-1β（IL-1β），interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in peripheral blood of three groups of rats were detected by ELISA kit. The levels of glutathione peroxidase（GSH-PX），superoxide dis－mutase（SOD） and malondialdehyde（MDA） in small intestine tissue were detected by ELISA kit. The expression level of apoptotic protein in small intestine tissue of three groups of rats was analyzed by Western blot. The apoptotic index of small intestinal villus cells was analyzed by TUNEL staining. Results：Compared with sham-operated group，the levels of inflammatory factors（IL-1β，IL-6 and TNF-α） and MDA in peripheral blood significantly increased，but GSH-PX and SOD level decreased significantly in small in－testine of rats in model group and SIRT1 group（P<0.05）. Compared with the model group，the levels of inflammatory factors（IL-1β，IL-6 and TNF-α） and MDA in peripheral blood in SIRT1 group decreased significantly，but GSH-PX and SOD level increased sig－nificantly（P<0.05）. Compared with sham-operated group，the expression of Caspase-3 and Bax in intestinal tissue of model group and SIRT1 group increased significantly，while the expression of Bcl-2 decreased significantly（P<0.05）. Compared with model group，the expression of Caspase-3 and Bax in small intestine tissue of SIRT1 group decreased significantly，while the expres－sion of Bcl-2 increased significantly（P<0.05）. Compared with the model group，the apoptotic index of intestinal epithelial cells in SIRT1 group decreased significantly（P<0.05）. Conclusion：Overexpression of SIRT1 can protect small intestinal tissues by reducing the levels of inflammation，oxidative stress and cell apoptosis in rats with small intestinal ischemia-reperfusion，which provides some guidance for clinical practice.