法舒地尔可能通过PI3-K/Akt信号通路抑制大鼠脑缺血/再灌注区神经元的凋亡  

Fasudil inhibits neuronal apoptosis after cerebral ischemia/reperfusion injury possibly through the PI3-K/Akt signal pathway

作　　者：吴建华[1] 谢立新[1] 方芳[1] 方云祥[1] 

机构地区：[1]中南大学药学院药理学教研室,湖南长沙410078

出　　处：《中国药理学通报》2008年第12期1569-1573,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学资金资助项目(No30672457)

摘　　要：目的探讨法舒地尔对大鼠脑缺血/再灌注损伤神经元是否具有抗凋亡作用并探讨其抗凋亡机制。方法大脑中动脉线栓法制作大鼠局灶性脑缺血/再灌注损伤模型。运用TUNEL法检测大鼠脑缺血/再灌注区神经细胞的凋亡,免疫组化法检测Bcl-2、Bax、Caspase-3蛋白的表达,Western blot法检测Akt以及Rho激酶特异性底物蛋白MYPT的磷酸化表达。结果法舒地尔能明显减少TUNEL染色阳性细胞数,增加Bcl-2的表达,降低Bax、Caspase-3的表达,升高Akt的磷酸化水平以及降低MYPT的磷酸化水平。结论①法舒地尔能减少大鼠脑缺血/再灌注区神经细胞凋亡。②法舒地尔的抗凋亡机制可能与其抑制Rho激酶活性,进而激活PI3-K/Akt传导通路有关。Aim To investigate the effects of fasudil on neuronal apoptosis after cerebral ischemia/reperfusion （I/R） injury in rats. Method Focal cerebral ischemia/reperfusion model in rats was made by transient occlusion of the middle cerebral artery for 90 minutes followed by 24 h reperfusion. The number of neural apoptotic cells was measured by the method of TUNEL staining; Bcl-2, Bax, Caspase-3 protein expressions were observed by immunohistochemical staining; the expression of phospho-MYPT and phospho-Akt protein was determined by Western blot. Result Compared with the MCAO group,fasudil could decrease the number of neural apoptotic ceils, upregulate the expression of Bcl-2 and phospho-Akt protein and inhibit the expression of Bax, Caspase-3 and phospho-MYPT protein significantly （ P 〈 0. 05 ）. Conclusions could significantly suppress cerebral ischemia/reperfusion The effect of fasudil against （1） Fasudil neuronal apoptosis after （I/R） injury in rats. （2） neuronal apoptosis might be correlated with the inhibition of the activity of Rho kinase and the activation of PI3-K/Akt signal pathway.

关 键 词：法舒地尔 脑缺血 凋亡 

分 类 号：R-332[医药卫生] R322.81