胡黄连苷Ⅱ通过抑制cyto C/caspase-9/caspase-3通路发挥神经保护作用

摘要

Aim To investigate the neuroprotective effect of picroside Ⅱ(PIC)on cyto C/caspase-9/caspase-3 signal pathway following ischemia/reperfusion(I/R)injury in rats.Methods Atractyloside(Atr)was selected as negative control,cyclosporin A(CsA)was selected as positive control,and PIC was selected as the treatment medicine.The I/R model was made by inserting a monofilament suture into internal carotid artery for 2 h,and then reperfused for 24 h.The cerebral infarction volume was detected by TTC staining,and the expression of cyto C,caspase-9 and caspase-3 were determined by immunohistochemical assay and Western blot.Results In model group,the cerebral infarct volume was obviously large;the expression of cyto C,caspase-9 and caspase-3 was increased significantly more than that in sham group(P<0.05).In PIC group,the cerebral infarct volume was significantly improved;the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in model group(P<0.05).In Atr+PIC group,the rat infarction volume was reduced,and the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in Atr group(P<0.05).Conclusion The mechanism of PIC inhibiting neuron apoptosis in focal cerebral I/R rats might be through down-regulating the expression of cyto C,caspase-9 and caspase-3.%目的 研究胡黄连苷Ⅱ对大鼠脑缺血/再灌注过程中cyto C/caspase-9/caspase-3信号通路的影响及其神经保护作用机制.方法 环孢素(CsA)和苍术苷(Atr)分别作为cyto C阳性对照和阴性对照,改良Longa法制备缺血2 h再灌注24 h大鼠脑缺血/再灌注(I/R)模型.再灌注24 h后,TTC染色观察脑梗死体积;免疫组织化学和Western blot检测cyto C、caspase-9、caspase-3表达水平.结果 模型组大鼠脑缺血/再灌注后TTC显示染色脑梗死体积明显增加;免疫组织化学和Western blot显示cyto C、caspase-9、caspase-3表达水平较假手术组明显增多(P<0.05).治疗组大鼠TTC显示脑梗死体积缩小;免疫组化和Western blot显示cyto C、caspase-9、caspase-3表达水平与模型组相比明显降低(P<0.05).与Atr组相比,Atr+胡黄连苷Ⅱ组大鼠脑梗死体积缩小,免疫组化和Western blot显示cyto C、caspase-9、caspase-3表达水平减弱(P<0.05).结论 胡黄连苷II抑制缺血/再灌注损伤大脑神经凋亡的机制可能与下调cyto C/caspase-9/caspase-3信号通路蛋白有关.