法舒地尔预处理对大鼠脑缺血再灌注损伤细胞色素C和caspase-3表达的影响

目的研究法舒地尔对大鼠局灶性脑缺血再灌注损伤细胞色素C（CytC）和caspase-3蛋白表达的影响,探讨其脑保护机制。方法线栓法制作大鼠中动脉缺血再灌注损伤模型。成年雄性SD大鼠120只随机分成3组：假手术组（Sham组）、脑缺血再灌注模型组（Mod组）、法舒地尔干预组（Fas组）,再分为再灌注3h、12h、24h和48h,以及TTC染色组5个亚组,每组8只大鼠。缺血再灌注后进行神经功能缺损评分（NDS）,免疫组织化学方法检测脑组织中CytC蛋白、cas-pase-3的表达,TTC染色测量鼠脑梗死体积并计算百分比。结果①Sham组大鼠无神经功能缺损,NDS评分为0,TTC染色亦未见脑组织梗死;Mod组和Fas组大鼠均有明显的神经功能缺损,TTC染色亦可见明显的脑组织梗死;但与Mod组相比,Fas组神经功能缺损少、NDS评分低（P〈0.01）,脑梗死体积减小（P〈0.05）。②与Sham组相比,脑缺血再灌注后,Mod组和Fas组大鼠脑组织CytC和caspase-3的表达显著升高（P〈0.01）,其中CytC表达高峰出现在12h,caspase-3表达高峰出现在24h;Fas组和Mod组间比较显示Fas组CytC和caspase-3的表达又显著低于Mod组（P〈0.01）。结论①法舒地尔能减轻大鼠脑局灶性缺血再灌注引起的神经功能缺损,减小脑梗死体积。②部分抑制脑缺血再灌注引起的CytC和caspase-3表达增加可能是法舒地尔的脑保护机制之一。

Effects of fasudil on the expression of cytochrome c and caspase-3 in rats with focal cerebral ischemia reperfusion injury

Objective To investigate the effect of fasudil on the expression of cytochrome c and caspase-3 in rats with focal cerebral ischemia reperfusion injury.Methods 120 male SD rats were randomly divided into 3 groups：sham operation group（Sham group）,ischemia reperfusion model group（Mod goup）,group treated by fasudil（Fas group）;according to the reperfusion time,each group was randomly divided into five subgroups,each subgroup had eight rats.The middle cerebral artery occlusion（MCAO） models were established with the method of intraluminal suture occlusion.After ischemia reperfusion,the neurologic deficit score（NDS） was evaluated,the expression of cytochrome c and caspase-3 was detected by immunohistochemistry,and the volume of cerebral infarction was observed by the TTC stain.Results ①There were no neurologic deficits and cerebral infarction in rats of the Sham group,while there were significant neurologic deficits and cerebral infarction in rats of the Mod group and Fas group.Compared to Mod group,the NDS and the cerebral infarct volume were significantly decreased in Fas group.②Compared to the Sham group,the positive expression of cytochrome c and caspase-3 were significantly increased in Mod group and Fas group.the positive expression of cytochrome c and caspase-3 respectively peaked at 12h and 24h.The positive expression of cytochrome c and caspase-3 were significantly lower in Fas group than in Mod group（P0.01）.Conclusion ①Fasudil can reduce neurologic deficits and the volume of the cerebral infarct in rats with focal cerebral ischemia reperfusion.②Fasudil could inhibit the expression of cytochrome c and caspase-3.This may be the mechanism of fasudil in cerebral protection.