Effect of atorvastatin preconditioning on intestinal ischemia-reperfusion injury in mice and the relationship with PI3K/Akt signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective:To investigate the effect of atorvastatin preconditioning on intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) signaling pathway.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), I/R group, atorvastatin preconditioning group (A group), atorvastatin plus PI3K inhibitor LY294002 group (AL group). Atorvastatin 10 mg/kg was given by intragastric gavage for 3 consecutive days in A and AL groups, and in addition LY294002 0.3 mg/kg was intraperitoneally injected at 30 min before the last administration of atorvastatin in AL group.Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 45 min followed by 2 h reperfusion in anesthetized mice.The superior mesenteric artery was only isolated but not clamped in S group.The mice were sacrificed at the end of reperfusion, and small intestinal tissues were taken for determination of the pathological changes with a light microscope after HE staining and for determination of wet to dry weight ratio(W/D ratio) and expression of PI3K, phosphorylated Akt (p-Akt), autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3Ⅰ (LC3Ⅰ) and LC3Ⅱ.The intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression (LC3Ⅱ/LC3Ⅰ) was calculated. Results:Compared with S group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in I/R, A and AL groups ( P<0.05). Compared with I/R group, Chiu′s scores and W/D ratio were significantly decreased, the expression of PI3K and p-Akt was up-regulated, the expression of Beclin-1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in A group ( P<0.05). Compared with A group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in AL group ( P<0.05). Conclusion:Atorvastatin preconditioning can mitigate intestinal I/R injury in mice, and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.