余丹枫　周格知　童民锋

[摘要] 目的 研究鹽酸法舒地尔对于动脉瘤性蛛网膜下腔出血（aSAH）患者介入栓塞治疗后Rho-激酶的调控及脑血管痉挛的预防作用。 方法 收录我院于2010年6月～2016年5月aSAH患者43例，均行介入栓塞治疗处理动脉瘤，术后分别应用盐酸法舒地尔或尼莫地平进行SAH后脑血管痉挛的预防治疗，测定不同时间段脑脊液Rho-激酶mRNA含量及相应时间段大脑中动脉平均流速，分析盐酸法舒地尔对于不同病程aSAH后Rho-激酶的调控和对脑血管痉挛的预防作用。 结果 盐酸法舒地尔组及尼莫地平组在治疗14 d后GCS评分均有显著改善，两组病例Rho-激酶在SAH后1周内均逐渐升高，在第2周下降，相比尼莫地平组，盐酸法舒地尔组在第3、7和14天Rho-激酶的浓度更低（P<0.05），且在相同时间点，盐酸法舒地尔组能够更有效降低大脑中动脉流速（P<0.05）。 结论 Rho-激酶在aSAH后1周内逐渐升高，在第2周下降，盐酸法舒地尔能够有效的抑制aSAH后Rho-激酶的表达，降低Rho-激酶在脑脊液中的浓度，从而降低相应时间段的大脑中动脉平均流速，其对脑血管痉挛的预防效果优于尼莫地平。

[关键词] 动脉瘤性蛛网膜下腔出血；介入栓塞；Rho-激酶；脑血管痉挛；盐酸法舒地尔；尼莫地平

[中图分类号] R743.3 [文献标识码] A [文章编号] 1673-9701（2018）20-0013-05

Study on regulation of fasudil hydrochloride in Rho-kinase after interventional embolization of aneurysm subarachnoid hemorrhage and its relationship with cerebral vasospasm

YU Danfeng ZHOU Gezhi TONG Minfeng CHEN Junliang LI Zhengyang YU Kaijie YUAN Jianlie

Jinhua Central Hospital in Zhejiang Province， Jinhua 321000， China

[Abstract] Objective To study the regulation of fasudil hydrochloride on Rho-kinase after interventional embolization of aneurysm subarachnoid hemorrhage and its preventive effect on cerebral vasospasm. Methods 43 patients with aSAH in our hospital from June 2010 to May 2016 were enrolled in this study. All patients underwent embolization to treat aneurysms. Patients were treated with fasudil hydrochloride or nimodipine after surgery for the prevention and treatment of cerebral vasospasm after SAH. The levels of Rho-kinase mRNA in cerebrospinal fluid and the average velocity of middle cerebral artery were measured at different time points. The effect of fasudil hydrochloride on the regulation of Rho-kinases and the prevention on cerebral vasospasm after aSAH with different courses of disease was analyzed. Results GCS scores of fasudil hydrochloride group and nimodipine group were significantly improved after 14 days of treatment. Rho-kinases in both groups increased gradually in the first week after SAH and decreased in the second week.The concentration of Rho-kinases in fasudil hydrochloride group on day 3， 7 and 14 was lower than that of the nimodipine group（P<0.05）. At the same time point， the fasudil hydrochloride group was more effective in reduce middle cerebral artery velocity（P<0.05）. Conclusion Rho-kinases gradually increase within 1 week after aSAH and decrease at the second week. Fasudil hydrochloride can effectively inhibit the expression of Rho-kinase after aSAH and decrease the concentration of Rho-kinase in cerebrospinal fluid and thus reduce the median cerebral artery velocity at the corresponding time， which is superior to nimodipine in the prevention of cerebral vasospasm.

[Key words] Aneurysmal subarachnoid hemorrhage； Interventional embolism； Rho-kinase； Cerebrovascular spasm； Fasudil hydrochloride； Nimodipine

蛛网膜下腔出血（SAH）是神经外科常见病，根据病因可分为创伤性蛛网膜下腔出血（tSAH）和自发性蛛网膜下腔出血（sSAH）。其中动脉瘤性蛛网膜下腔出血（占70%～80%）是自发性蛛网膜下腔出血的主要病因。脑血管痉挛（CVS）是指蛛网膜下腔出血后大脑底部大容量动脉管腔的迟发性缩窄，作为蛛网膜下腔出血（SAH）最严重的并发症之一，可引起弥漫性脑水肿和迟发性缺血性神经损伤，是SAH 致死和致残的首要原因[1]。因为SAH后脑血管痉挛的严重性和高发生率，其始终是SAH治疗中的重中之重，除了常规的3H治疗，目前临床当中最常用的药物是尼莫地平，临床研究证实其作为钙离子通道阻滞剂，有缓解脑血管痉挛的作用，经颅多普勒超声也证实其能改善SAH后脑血流[2]，但是脑血管造影并未能显示出其明显缓解血管痉挛的作用[3]。……