Role of extracellular signal-regulated kinase in neuronal apoptosis of hippocampns induced by global cerebral ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of extracellular signal-regulated kinase in neuronal apoptosis of hippoeampus induced by global cerebral ischemia-reperfusion in rats.Methods Ninety healthy male SD rats weighing 280-320 g were randomly divided into 3 groups(n=30 each):groupI sham operation(S);groupⅡI/ R and group Ⅲ PD98059+I/R(PD).The animals were anesthetized with intraperitoneal 1% pentobarbital 40 mgkg.Global cerebral I/R was produced by 4-vessel occlusion method.Bilateral vertebral arteries were electrically cauterized and bilateral common carotid arteries were clamped for 5 min.Clamping was then released for reperfusion in group Ⅱ and Ⅲ.In group Ⅲ PD98059(a specific ERK inhibitor)O.3 mg/kg was injected iv before carotid artery clamping.Five animals in each group were sacrificed at 2,6,12,24,48 and 72 h of reperfusion and their brains were removed and cut into sections which were stained with HE and examined under microscope(400 times magnified).Neuronal apoptosis in hippieampal Cal and CA3 regions were detected by TUNEL assay.Apoptotic index(AI) was calculated.Phosphorylated ERK(p-ERK)and phosphorylated Bad (p-Bed)expression was assessed by immuno-histochemistry.Results (1)Hippoeampal pyramidal cells were orderly distributed and morphologically intact in group S but unevenly distributed with widened intercellular space,shrinked cell body and condensed nuclei in I/R group.The I/R induced changes were worse in PD group.(2)AI in Cal and CA3 region was significantly higher in PD group than in I/R group.(3)The p-ERK expression in Cal region was signiticanfly decreased at 2,6,12 h of reperfusion in I/R(Ⅲ)and PD groups(Ⅲ)as compared with group S(I),while p-ERK expression in CA3 region was significantly lower at 2,6,12,24 h of reperfusion in PD group(Ⅲ)than in S(I)and I/R group(Ⅱ).(4)The p-Bed expression in Cal and CA3 regio was signi ficantly lower during reperfusion in PD group than in I/R group and was lowest in group S(I).Conclusion Cerebral isehemia reperfusion can decrease the p-ERK expression and then leads to the dephosphorylation of Bed(a member of Bel-2 protein family),which induced the apeptosis in hippoeampal neurons.