法舒地尔对蛛网膜下腔出血大鼠血管保护作用的机制研究

Vascular protective effect of fasudil after subarachnoid hemorrhage in rats

目的:通过建立大鼠实验性蛛网膜下腔出血模型,探讨法舒地尔对蛛网膜下腔出血后血管的保护作用及机制。方法:将48只大鼠随机分为假手术对照组(Control group,C组)、蛛血组(SAHgroup,S组)和法舒地尔治疗组(Treatment group,T组),通过枕大池单次注血法建立大鼠蛛网膜下腔出血模型,分别于1d、3d、7d和14d采用光镜观察基底动脉形态变化,测量基底动脉管径和管壁厚度。运用免疫组化SP法检测基底动脉上内皮型-氧化氮合成酶(Endothelial nitric oxide synthase,eNOS)的表达。结果:S组大鼠的基底动脉痉挛从建模后1d开始出现,3d后达到高峰,7d后明显减轻;eNOS的表达在各时相点明显减弱。T组基底动脉的管径和管壁厚度在建模后3d、7d与S组有统计学差异(P<0.05);同时eNOS的表达在3d、7d、14d较S组增强(P<0.05)。结论:法舒地尔可以有效缓解SAH后的脑血管痉挛,增加eNOS在动脉管壁上的表达可能是其重要的作用机制之一。

Objective：To explore the vascular protective effects and mechanism of fasudil in rats after experimental subarachnoid hemorrhage.Methods：Forty-eight rats were divided into sham-operated control group,subarachnoid hemorrhage group and treatment group.Model induced by autologous blood injection into cisterna magna,and rats were killed on day 1,day 3,day 7 and day 14 after subarachnoid hemorrhage.Morphological change of basilar artery was observed by light microscopy,diameter and wall thickness of basilar artery were measured respectively.eNOS expression in basilar artery was detected by immunohistochemical SP method.Results：Vasospasm of basilar artery initiated on day 1,reached its peak on day 3,and mitigated on day 7 after SAH.eNOS expression decreased at each time point in SAH group.Compare with SAH group,diameter and wall thickness of basilar artery were significantly reduced on day 3 and day 7 in treatment group（P〈0.05）,and eNOS expression also statistically increased on day 3,day 7 and day 14（P〈0.05）.Conclusion：Fasudil can effectively relieve post-SAH cerebral vasospasm.Upregulation of eNOS expression in the arterial wall might be one of important mechanisms.