Effect Of Atorvastatin Preconditioning On Intestinal Ischemia-Reperfusion Injury In Mice And The Relationship With PI3K/Akt Signaling Pathway

Objective: To investigate the effect of atorvastatin preconditioning on intestinal ishemia-reperfusion（I/R）injury in mice and its relationship with PI3K/Akt signaling pathway.Methods: Twenty-four healthy male C57BL/6 mice aged 6-8 weeks and weighing 18-22 g,were divided into 4 groups（n=6）using a random number table method: sham operation group（S group）,I/R group,atorvastatin preconditioning group（A group）,atorvastatin plus PI3K/Akt inhibitor LY29400（AL group）.In group A and AL,atorvastatin 10 mg/kg was gavage continuously for 3 d,and LY294002 0.3mg/kg was intraperitoneally injected 30 min before the last gavage of atorvastatin in AL group.Then,a model of intestinal ischemia-reperfusion injury was established,and the occlusion of mesenteric artery was treated by perfusion,and the duration of perfusion was 2 hours.In S group,only the separation of mesentery was performed,and the artery was not clipped.The mice were sacrificed at the end of reperfusion and their small intestine tissues were taken for determination of the pathological chanages with a light microscope after HE staining,and for determination of wet to dry weight ratio（W/D）and Western blot was used to detect the expression of PI3 K and phosphorylate Akt（p-Akt）,autophagy-related proteins Beclin-1,microtubule-associated protein 1 light chain 3 Ⅰ（LC3 Ⅰ）and LC3 Ⅱ;The ratio of LC3 Ⅱ to LC3 Ⅰ expression level was calculated（LC3 Ⅱ /LC3Ⅰ）.Results: As compared with the S group,Chiu’s scores,W/D ratio were significantly increased,PI3 K and p-Akt protein expression decreased,Beclin-1and LC3Ⅱ/LC3Ⅰ increased in the IR group,A group,and AL group（P<0.05）.As compared with the I/R group,Chiu’s scores,W/D ratio decreased and PI3 K and p-Akt protein expression increased,Beclin-1and LC3Ⅱ/LC3Ⅰ decreased in the A group and AL group（P<0.05）.As compared with the A group,Chiu’s scores,W/D ratio increased and PI3 K and p-Akt protein expression decreased,Beclin-1and LC3Ⅱ/LC3Ⅰincreased in the AL group（P<0.05）.Conclusion: Atorvastatin preconditioning can mitigate intestinal I/R in mice and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.