Atorvastatin Attenuates Oxidative Stress Induced By Intestinal Ischemia-Reperfusion Injury Via Nrf2/HO-1 Pathway

Objective : To investigate the effects of atorvastatin on oxidative stress induced by Ischemia reperfusion(I /R)and nuclear factor erythroid like 2(Nrf2)/Heme oxygenase-1(HO-1)pathway.Methods:Twenty-four male C57BL/6 mice,weighing 18-22 g.Random number table method was used to divide into 4 groups(n=6): sham operation group(S group),ischemia reperfusion group(I/R group),atorvastatin group(ATV group)and Nrf2 inhibitor ML385+atorvastatin group(AM group).The model of intestinal ischemia-reperfusion injury in mice was established by clamping the superior mesenteric artery for 45 minutes.ATV group and AM group were given atorvastatin10 mg/kg by gavage 3 days before modeling,and S group and I/R group were given equal volume normal saline by gavage;AM group was intraperitoneally injected with Nrf2 inhibitor ML385 30 mg/kg 1 hour before modeling.The mice were sacrificed after reperfusion,and the small intestine tissues were taken.The pathological results were observed under light microscope,and the degree of intestinal mucosal injury was scored by Chiu.The ratio of wet weight to dry weight(W/D)was calculated.The activity of superoxide dismutase(SOD)and contents of malondialdehyde(MDA)in intestinal tissue were detected by xanthine oxidase method and thiobarbituric acid condensation method.The expression levels of pathway-related proteins Nrf2 and HO-1 were determined by western blotting.Results :Compared with S group,Chiu score,W/D ratio,MDA content and the expression of Nrf2 and HO-1 were increased in the other three groups(P<0.05),while the activity of SOD was decreased(P<0.05);Compared with the group I/R,the Chiu score,W/D ratio,MDA content were decreased,the SOD activity was increased,the expression of Nrf2 and HO-1 were increased in group ATV(P<0.05),and the histopathological injury of small intestine decreased.There was no significant difference in the above indexes in AM group(P>0.05);Compared with the group ATV,the Chiu score,W/D ratio,MDA content were increased,the SOD activity was decreased,the expression of Nrf2 and HO-1 were decreased(P<0.05),and the histopathological injury of small intestine increased.Conclusion : Atorvastatin intervention can alleviate the oxidative stress injury of intestinal ischemia-reperfusion in mice,and the mechanism of this protective effect may be related to the activation of Nrf2/HO-1 signaling pathway.