Role of PI3K/Akt signaling pathway in mild head hypothermia-induced reduction of global cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in mild head hypothermia-induced reduction of global cerebral ischemiareperfusion (I/R) injury in rats.Methods Sixty male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 5 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,mild hypothermia + I/R group (group H),mild hypothermia + I/R + solvent control group (group DM),and mild hypothermia + I/R + PI3K inhibitor LY294002 group (group LY).Global cerebral I/R was induced by modified four-vessel occlusion method described by Pulsinelli.In H group,when the hippocampal temperature was decreased to 33℃ using nasopharyngeal cooling,the bilateral common carotid arteries were occluded for 15 min followed by reperfusion,and hippocampal hypothermia was maintained at 32.5-33.5 ℃ for 1 h.In DM and LY groups,DMSO and LY294002 5 μl were injected into the left ventricle,respectively,and 20 min later the other procedures were similar to those previously described in group H.At 8 h of reperfusion,6 rats were sacrificed,and hippocampal specimens were obtained to detect the expression of pFoxO3a,Bcl-2 and Bax (by immuno-histochemistry).The expression of phosphor-Akt (p-Akt) was determined by Western blot.Results Compared with group S,the expression of p-Akt,pFoxO3a and Bcl-2 was significantly up-regulated in I/R,H and DM groups,the expression of Bcl-2 was down-regulated,and the ratio of Bcl-2/Bax was increased in H and DM groups,and the ratio of Bcl-2/Bax was decreased in I/R and LY groups.Compared with group I/R,the expression of p-Akt,pFoxO3a and Bcl-2 was significantly up-regulated,the expression of Bcl-2 was down-regulated,and the ratio of Bcl-2/ Bax was increased in H and DM groups.Compared with H and DM groups,the expression of p-Akt,pFoxO3a and Bcl-2 was down-regulated,the expression of Bax was up-regulated,and the ratio of Bcl-2/ Bax was decreased in group LY.Conclusion PI3K/Akt signaling pathway is involved in reduction of global cerebral I/R injury by mild head hypothermia in rats.