选择性内皮素受体A拮抗剂改善高血压大鼠脑白质病变  

Selective inhibition of endothelin receptor A improves white matter lesions in hypertensive rats

作　　者：王迪龙[1] 邱宝山 林晶[1] 蔡颖 范玉华[1] WANG Di-long;QIU Bao-shan;LIN Jing;CAI Ying;FAN Yu-hua(Department of Neurology, The First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510030, China)

机构地区：[1]中山大学附属第一医院神经内科,广东广州510030

出　　处：《中国病理生理杂志》2018年第5期878-883,共6页Chinese Journal of Pathophysiology

基　　金：广东省科技计划项目(No.2015 A030302013)

摘　　要：目的:观察选择性内皮素受体A(endothelin receptor A,ETRA)拮抗剂是否能够改善高血压大鼠脑白质病变的严重程度,并探讨其机制。方法:33只Sprague-Dawley大鼠随机分为假手术(sham)组(n=9)、治疗(treatment)组(n=12)和溶剂对照(placebo)组(n=12),其中治疗组和溶剂对照组复制易卒中型肾血管性高血压改良的2VO(stroke-prone renovascular hypertensive rats-modified 2 vessel occlusion,RHRSP-modified 2VO)大鼠模型,17~20周分别给予安倍生坦和安慰剂灌胃并每周监测收缩压,20周对大鼠进行Morris水迷宫实验检测认知功能,ELISA法定量分析各组大鼠皮层、胼胝体和尾壳核的内皮素1(endothelin-1,ET-1)的蛋白表达水平,组织病理学检测是否存在脑白质病变并评价严重程度,同时用免疫荧光法观察内皮素1与血管的关系。结果:与溶剂对照组比较,治疗组收缩压的差异不明显,逃避潜伏期缩短(P<0.05),穿越平台次数增多(P<0.05),胼胝体和尾壳核的ET-1蛋白表达水平均下降(P<0.05),脑白质病变严重程度降低(P<0.05),ET-1与血管结合程度降低。结论 :选择性拮抗血管平滑肌上的ETRA能够减轻高血压大鼠的脑白质损伤,并改善认知功能。AIM： To observe whether selective inhibition of endothelin receptor A（ ETRA） improves white matter lesions（ WMLs）,and explore the mechanism. METHODS： Sprague-Dawley rats（ n = 33） were randomly divided into sham operation group（ n = 9）,treatment group [stroke-prone renovascular hypertensive rats-modified 2 vessel occlusion（ RHRSP-modified 2 VO） ＋ ambrisentan（ n = 12） ] and placebo group [RHRSP-modified 2 VO ＋ vehicle（ n =12） ]. Drug and vehicle administration was performed from 17th to 20th week and monitoring of systolic arterial pressure was performed weekly. Morris water maze test was conducted to evaluate the function of cognition. The protein levels of endothelin-1（ ET-1） in the cortex,corpus callosum and caudate putamen were quantitatively analyzed respectively. The severity of WMLs and the relationship between ET-1 and vessels were observed by the method of histopathology. RESULTS：The difference of systolic arterial pressure between treatment group and placebo group was not significant. The animals in treatment group exhibited shorter escape latency（ P〈0. 05）,more times of crossing platform（ P〈0. 05）,lower level of ET-1 in corpus callosum and caudate putamen（ P〈0. 05）,respectively,improved WMLs severity（ P〈0. 05） and lower binding level of ET-1 to vessels compared with the placebo group. CONCLUSION： Selective inhibition of endothelin receptor A improves the severity of WMLs and ameliorates the cognitive function.

关 键 词：脑白质病变 高血压 内皮素1 认知障碍 内皮素受体A 

分 类 号：R741.02[医药卫生—神经病学与精神病学] R363[医药卫生—临床医学]