Role of TAK1 mediated cell autophagy after global cerebral ischemia-reperfusion in rats / 临床麻醉学杂志

ABSTRACT

Objective To study the effects of TGFβ-activated kinase-1 (TAK1)mediated cell autophagy after global cerebral ischemia-reperfusion (IR ) in rats.Methods Seventy-two male Kunming rats were randomly divided into six groupscontrol group (group C),sham operation group (group S),ischemia-reperfusion group (group IR),TAK1 shRNA lentivirus group (group T),nega-tive lentivirus group (group Y)and normal saline group (group NS)(n = 12 each).The rats in groups T,Y and NS received cerebral ventricles injection of TAK1 shRNA lentivirus,negative lenti-virus and normal saline 10 μl two weeks before preparing animal model.Using thread embolism of the right middle cerebral artery occlusion (MCAO)to cause focal ischemia for 2 h and released for 24 h for reperfusion in groups IR,T,Y and NS.The common carotid arteries were separated but not liga-ted in group S,the rest of the procedure as the same as group IR.The rats of each group were evalua-ted by neurological severity scores (NSS)24 h after reperfusion,the cerebral infarct volume was measured with the method of TTC and the expression of TAK1,LC3Ⅱ/LC3Ⅰ,Beclin1 and p62 pro-tein in rat hippocampus were determined by using Western blot.Results The infarct volume and NSS in groups IR,T,Y and NS were significantly higher than those in group C (P <0.05).The infarct volume and NSS in group T were significantly lower than those in group IR (P <0.05).TAK1 pro-tein of hippocampus in groups IR,Y and NS was significantly higher than that in group C (P <0.05).TAK1 protein of hippocampus in group T were significantly lower than that in group IR (P <0.05).LC3Ⅱ/LC3 Ⅰand Beclin1 protein of hippocampus in groups IR,T,Y and NS were signifi-cantly higher than those in group C,and the p62 protein of hippocampus in groups IR,T,Y and NS was significantly lower than that in group C (P <0.05).The LC3 Ⅱ/LC3 Ⅰand Beclin1 in group T were significantly lower than those in group IR,and the p62 protein of hippocampus in group T was significantly higher than that in group C (P < 0.05 ).Conclusion TAK1 mediated cell autophagy takes part in the mechanism of brain ischemia-reperfusion injury in rats.