Rho激酶抑制剂对脑出血大鼠的脑保护作用及其对eNOS表达水平的影响  

The brain protection effects and the eNOS expression level impact of the Rho kinase inhibitor on ICH rats

作　　者：李雪莹 岳孟孟 娄晓丽 赵迎春 Li Xueying;Yue Mengmeng;Lou Xiaoli(Department of Neurology,Shanghai Songjiang Central Hospital Affiliated to Nanjing Medical University,Shanghai 201699)

机构地区：[1]南京医科大学附属上海松江中心医院神经内科

出　　处：《卒中与神经疾病》2019年第5期535-540,共6页Stroke and Nervous Diseases

基　　金：上海市卫计委科研课题(201540141)

摘　　要：目的观察Rho激酶抑制剂的脑保护作用及对eNOS表达水平的影响。方法 140只SD大鼠采用自体不凝动脉血注入法建立脑出血模型,并随机分为5组,即假手术组、脑出血(ICH)1 d组、脑出血(ICH)3 d组、法舒地尔(Fasudil)1 d组、法舒地尔(Fasudil)3 d组;按时间点断头取脑,取血肿周围组织,用干湿重法测量大鼠脑含水量,TUNEL荧光染色观察脑细胞凋亡情况,ELISA法检测脑组织中炎症因子TNF-α的表达水平,western blot法检测ROCK2和eNOS的表达水平变化。结果大鼠脑出血1、3 d组血肿周围组织ROCK2和eNOS蛋白表达水平、脑组织含水量、IL-6和TNF-α相对水平、凋亡细胞阳性率较假手术组明显增高(P<0.05);法舒地尔1、3 d组血肿周围组织的ROCK2、eNOS蛋白表达水平、脑组织含水量、IL-6、TNF-α相对水平、凋亡细胞阳性率较脑出血1、3 d组明显降低(P<0.05)。结论 Rho激酶抑制剂法舒地尔能够减轻脑出血大鼠的脑水肿、炎症反应和神经元凋亡,起到了一定的保护作用,其机制可能与eNOS有关。Objective To observe the brain protection effects and the eNOS expression level impact of the Rho kinase inhibitor on ICH rats.Methods One hundred and forty rats were randomly divided into 5 groups:sham-operated group,ICH 1,3 d group and Fasudil 1,3 d groups.Their brains were taken out at planned time.The tissue around the hematoma was taken,the brain water content was measured by dry-wet weight method,the apoptosis was observed by TUNEL fluorescence,whilethe level of IL-6,TNF-α in brain tissue was detected by ELISA kit.The expression levels of ROCK2 and eNOS were examined by Western blot.Results The expression levels of ROCK2 and eNOS,brain tissue water content,IL-6,TNF-α relative content and apoptosis rate in the perihematomal tissue of rats in ICH 1,3 d groups were significantly higher than those in the sham operation group(P<0.05).After fasudil treatment,the expression levels of ROCK2 and eNOS,the levels of IL-6 and TNF-α,brain tissue water content and apoptosis rate in the perihematomal tissue of Fasudil 1,3 d groups were significantly lower than those in the perihematomal tissue of ICH 1 and 3 d groups(P<0.05).Conclusion The Rho kinase inhibitor(fasudil) cold alleviate brain edema,inflammatory response and neuronal apoptosis in rats with cerebral hemorrhage,and its mechanism might be related to eNOS.It ould play a protective role and provide new therapeutic direction for the treatment of cerebral hemorrhage.

关 键 词：脑出血 细胞凋亡 炎症 脑水肿 Rho激酶2 内皮型一氧化氮合成酶 

分 类 号：R743.34[医药卫生—神经病学与精神病学]