PI3K/AKT/GSK-3β信号在脑缺血预处理中的作用及对海马细胞凋亡的影响  

Role of PI3K/AKT/GSK-3β Signal in Cerebral Ischemic Preconditioning and Its Impact on Apoptosis of Hippocampus Cells

作　　者：张慧[1] 姜咏梅[1] 尹琳[1] 

机构地区：[1]大连医科大学附属第二医院神经内科,大连116027

出　　处：《华中科技大学学报（医学版）》2011年第4期408-412,428,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的研究脑缺血预处理(CIPC)中PI3K/AKT/GSK-3β信号通路调节变化及对海马细胞凋亡的影响。方法制作脑缺血、CIPC及LY294002干预模型。进行神经功能缺损评分;TTC染色计算脑梗死体积;TUNEL法检测海马细胞凋亡;Western blot检测p-PDK1、AKT、p-AKT、GSK-3β、p-GSK-3β(ser9)、Mc-l1的蛋白表达,RT-PCR检测GSK-3β的转录。结果①与脑缺血组比较,CIPC组在神经功能缺损评分、脑梗死体积、细胞凋亡、GSK-3β蛋白表达及转录水平均降低(均P<0.05),但脑缺血组与LY294002组比较,上述各检测值差异均无统计学意义(均P>0.05);②与脑缺血组比较,CIPC组的p-PDK1、p-AKT、p-GSK-3β(ser9)、Mc-l1的蛋白表达均增高,LY294002组各蛋白表达较CIPC组均降低(均P<0.05),LY294002组与脑缺血组比较各蛋白表达差异均无统计学意义(均P>0.05)。结论脑缺血预处理降低GSK-3β的转录和蛋白表达,增加p-PDK1、p-AKT、p-GSK-3β(ser9)、Mc-l1的表达,减少神经元凋亡。LY294002可抵消脑缺血预处理的保护作用。Objective To study the effect of cerebral ischemic preconditioning（CIPC）on apoptosis of the hippocampus neurons and its possible relationship with PI3K/AKT/GSK-3β signal transduction pathway.Methods The ischemia,CIPC,and LY294002-pretreated intervention rat models were established.The neurological deficit scores were processed.The right hippocampi were drawn and stained with TTC.The volume of the cerebral infarction was calculated.The apoptosis of the hippocampus neurons was examined by using TUNEL apoptosis detection kit.The expression of p-PDK1,AKT,p-AKT,GSK-3β,p-GSK-3β（ser9）and Mcl-1 proteins was detected by using Western blot,and the expression of GSK-3β mRNA by RT-PCR,respectively.Results ①As compared with ischemia group,CIPC decreased the neurological deficit scores,the volume of the cerebral infarction,the protein expression of GSK-3β and the transcription of GSK-3β mRNA level（P〈0.05）,but there was no significant difference between ischemia group and LY294002-pretreated group（P〈0.05）;②In comparison with ischemia group,CIPC increased the expressions of p-PDK1,p-AKT,p-GSK-3β（ser9）,and Mcl-1 in ischemic hippocampi（P〈0.05）.In the LY294002-pretreated group,the protein expression of these factors was decreased as compared with CIPC group（P〈0.05）,but there was no significant difference between ischemia group and LY294002-pretreated group（P〈0.05）.Conclusion CIPC reduces the transcription and protein expression levels of GSK-3β,increases the expression levels of p-PDK1,p-GSK-3β（ser9）,p-AKT and Mcl-1,and decreases the apoptosis of neurons.LY294002 blocks the neuroprotective effects of CIPC.

关 键 词：脑缺血预处理 磷脂酰肌醇激酶-3/丝苏氨酸蛋白激酶通路 糖原合成酶激酶-3Β 髓细胞淋巴瘤-1 3-磷酸肌醇依赖性蛋白激酶-1 

分 类 号：R349.5[医药卫生—基础医学]