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  

Picroside Ⅱ plays a neuroprotective effect by inhibiting cyto C/caspase-9/caspase-3 signal pathway following ischemia/reperfusion injury in rats

作　　者：张红艳[1] 翟丽[1] 王婷婷[1] 李珊[1] 张艳辉[1] 郭云良[1] ZHANG Hong-yan ZHAI Li WANG Ting-ting LI Shan ZHANG Yan-hui GUO Yun-liang(Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao Shandong 266003,Chin)

机构地区：[1]青岛大学附属医院脑血管病研究所,山东青岛266003

出　　处：《中国药理学通报》2017年第5期668-674,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81274116)

摘　　要：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(Cs A)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。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.

关 键 词：胡黄连苷Ⅱ 脑 缺血/再灌注损伤 cyto C/caspase-9/caspase-3信号通路 神经保护 大鼠 

分 类 号：R-332[医药卫生] R284.1