Influences Of Cerebral Ischemia Preconditioning On Autophagy And Apoptosis In Rats With Focal Cerebral Ischemia-reperfusion Injury

Objective Influences of cerebral ischemia preconditioning on autophagy and apoptosisin rats with focal cerebral ischemia-reperfusion injury.Methods The middle cerebral artery ischemia preconditioning and ischemia-reperfusion model in rats were achieved by intraluminal filament embolism, the rats wererandomly divided into sham operated group, ischemia-reperfusion group and ischemiapreconditioning group. The reperfusion was performed at2h,6h,12h,24h,3d and5d.The neurological score was taken to evaluated the rats, the infarction volume wasmeasured by TTC staining, the morphological feature of neuron was observed by HEstaining, the level of Beclin-1, LC3-II, Bcl-2, Caspase-3were detected byimmunohistochemistry staining, the ultrastructure change of autophagy and apoptosiswere observed by transmission electron microscope.Results1Compared with sham operated group, neurological impairment, infarctionvolume and nerve cell injury were seen in ischemia-reperfusion group and ischemiapreconditioning group. Compared with ischemia-reperfusion group, ischemiapreconditioning group showed alleviated neurological impairment (P<0.05), reducedinfarction volume (P<0.05) and relieved nerve cell injury.2Compared with shamoperated group, ischemia-reperfusion group and ischemia preconditioning group ratsresulted in significant up-regulation of Beclin-1and LC3-II. While, compared withischemia-reperfusion group, ischemia preconditioning group rats resulted in significantdown-regulation of Beclin-1and LC3-II (P<0.05).3Compared with sham operatedgroup, ischemia-reperfusion group and ischemia preconditioning group rats resulted insignificant up-regulation of Bcl-2and Caspase-3. While, compared with ischemia-reperfusion group, ischemia preconditioning group rats resulted in significant up-regulation of Bcl-2(P<0.05) and down-regulation of Caspase-3(P<0.05).4There werenot number of autophagy and apoptosis in nerve cell of sham operated group bytransmission electron microscope. The formation of autophagolysosomes were detectedby TEM at2h after ischemia-reperfusion injury; at6h, enhanced presence ofautophagolysosomes and apoptosis were detected by TEM; the presence ofautophagolysosomes and apoptosis were significantly obvious at12~24h, until3d; at5d, there were still autophagy and apoptosis. Compared with ischemia-reperfusion group,ischemia preconditioning group represented lighten degree of autophagy and apoptosis.Conclusion1The nerve cell appeared autophagy and apoptosis after ischemia-reperfusion. There were obvious neurological impairment, infarction volume, nerve cellinjury, Beclin-1, LC3-II, Bcl-2and Caspase-3positive cells and formation ofautophagolysosomes and apoptosis after ischemia-reperfusion ingury.2Ischemiapreconditioning could protect nerve cell from autophagy and apoptosis through up-regulation of Bcl-2expression and down-regulation of Beclin-1, LC3-II and Caspase-3expression, alleviating neurological impairment, reducing infarction volume and relievingnerve cell injury.Figure19, Table6, Reference102...