活血通络方通过死亡受体通路抗神经元凋亡机制的研究

目的探讨大鼠脑缺血再灌注后死亡受体通路Fas相关死亡结构域蛋白(FADD)、凋亡蛋白酶(caspase)-8、caspase-3的表达及活血通络方的干预作用机制。方法将72只大鼠随机分成4组,即假手术组、模型组、活血通络组、尼莫地平组,每组18只,大脑中动脉栓塞再通法建立脑缺血再灌注模型,原位末端标记法检测凋亡神经元,免疫组织化学法检测FADD、caspase-8、caspase-3阳性细胞数。结果与假手术组比较,模型组神经元凋亡指数和FADD、caspase-8、caspas-3阳性细胞数均明显增多(P<0.01);与模型组比较,活血通络组和尼莫地平组神经元凋亡指数、FADD、caspase-8、caspase-3阳性细胞数均明显减少(P<0.05,P<0.01)。结论FADD、caspase-8和caspase-3在脑缺血再灌注损伤中发挥重要作用,活血通络方可减轻缺血再灌注所致神经元凋亡,其机制可能与抑制细胞凋亡死亡受体通路有关。

Study on the mechanisms of depressing neuron apoptosis by Huoxue Tongluo recipe through death receptors pathway

Objective To explore the expression of Fas-associated protein with death domain (FADD),caspase-8 and caspase-3 on death receptors pathway induced by cerebral ischemia-reperfusion (I/R) as well as the mechanisms of the interventional effect of Huoxue Tongluo recipe. Methods Rats were randomly divided into 4 groups,i.e.sham operation group,model group, Huoxue Tongluo group and nimodipine group.The model of cerebral ischemia/reperfusion(I/R) was established by middle cerebral artery occlusion and recanalization.Terminal deoxyribonucle otide transferase-mediated dUTP-biotin nick end labeling method was used to detect the apoptotic neurons.The positive neurons of FADD,caspase-8 and caspase-3 were detected by immunohisto-chemistry. Results Compared with sham operation group,the apoptotic index and FADD, caspase-8,caspase 3 positive neurons increased significantly in model group(P<0.01).Compared with model group,the apoptotic index and the FADD,caspase-8,caspase-3 positive neurons decreased markedly in Huoxue Tongluo group and nimodipine group(P<0.05,P<0.01).Conclusions FADD,caspase-8 and caspase-3 play important roles in the cerebral I/R injury.Huoxue Tongluo recipe could protect neurons from I/R injury by suppressing the death receptors pathway.