大鼠肝脏缺血再灌注时肝细胞凋亡与Bcl-2蛋白表达的关系

Relevance of hepatocellular apoptosis and expression of Bcl-2 protein in rats during hepatic ischemia-reperfusion.

目的 探讨肝脏缺血再灌注时肝细胞凋亡与Bcl 2蛋白表达的关系。方法 建立大鼠局部肝脏缺血再灌注模型 ,将 72只健康雄性Wistar大鼠随机分为正常组、假手术组和缺血再灌注组 ,采用免疫组织化学法测定再灌注后不同时相中肝组织Bcl 2蛋白含量 ,用末端脱氧核苷酸转移酶介导的三磷酸脱氧尿苷 (dUTP)缺口末端标记 (TUNEL)法和透射电镜观察肝细胞凋亡状态。结果 再灌注后 1、3、6、2 4h肝组织Bcl 2蛋白含量明显低于正常组及假手术组 ,并于 3～ 6h达到其最低值 ;再灌注后 1、3、6、2 4h肝细胞凋亡指数 (HAI)则明显高于正常组和假手术组 ,并于 3～ 6h达到高峰。再灌注后各时相中Bcl 2蛋白水平与HAI呈明显负相关。结论 在肝脏缺血再灌注时 ,Bcl 2蛋白表达水平异常下调 ,其抑制细胞凋亡的效能减弱 ,促使肝实质细胞凋亡增加 ,加重肝脏缺血再灌注损伤。

Objective To investigate the relcvance of hepatocellular apoptosis and the expression of Bcl-2 protein in rats during hepatic ischemia-reperfusion.Methods With a rat model of hepatic ischemia-reperfusion, 72 healthy male Wistar rats were randomly divided into 3 groups: normal group、sham-operation group and ischemia-reperfusion group. The Bcl-2 protein content in heaptic tissue was measured by immunohistochemical analysis. Moreover, the hepatocellular apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and electronmicroscropy.Results The content of Bcl-2 protein in ischemia-reperfusion group were markedly lower than that in the normal and sham-operation groups, Where as the hepatocellular apoptotic index (HAI) in ischemia-reperfusion group was markedly higher than that in the normal and sham-operation groups. The Bcl-2 protein reached its lowest and HAI value approached its peak level 3 to 6 hours after reperfusion. Moreover, In each phase of reperfusion, Bcl-2 protein level and HAI showed negative correlation significantly.Conclusion The down-regulation of the expression of Bcl-2 protein induces hepatocellular apoptosis during hepatic ischemia-reperfusion injury.