瑞舒伐他汀钙对慢性高血压大鼠脑白质病变及空间认知功能的影响  

Effect of rosuvastatin on white matter lesion in chronic hypertensive rats

作　　者：郑璐[1] 范玉华[1] 蓝琳芳[2] 姬晓昙 

机构地区：[1]中山大学附属第一医院神经科,教育部国家重点学科,卫生部国家临床重点专科,广东省重大神经疾病诊治研究重点实验室,广州510080 [2]香港中文大学威尔斯亲王医院内科与药物治疗系

出　　处：《中国神经精神疾病杂志》2015年第2期92-97,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学青年基金(编号:81000514);广东省自然科学基金项目(编号:s2013010015840)

摘　　要：目的探讨瑞舒伐他汀钙对慢性高血压大鼠的脑白质病变及其空间认知功能障碍的影响。方法雄性Sprague-Daw Iey大鼠49只,随机分为假手术组、高血压组和瑞舒伐他汀钙治疗组(10 mg/kg)。高血压组和瑞舒伐他汀钙治疗组采用双肾双夹法制作易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rat,RHRSP)模型,定期监测血压。水迷宫实验检测空间记忆功能;Luxol fast blue染色观察脑白质疏松程度;免疫荧光法观察额叶皮层β-淀粉样蛋白(β-amyloid,Aβ)在大脑皮层的沉积分布;原位末端转移酶标记染色法(Td T-mediated d UTP-biotin nick end labeling,TUNEL)观察额叶皮层细胞凋亡水平。结果 RHRSP大鼠造模后血压逐渐升高,明显高于假手术组(P<0.01);瑞舒伐他汀钙较高血压组逃避潜伏期时间明显缩短(P<0.01),3组大鼠跨越平台次数分别为(4.55±1.23)、(1.00±0.80)、(3.79±0.95),差异有统计学意义(P<0.01)。与高血压组相比,瑞舒伐他汀钙可改善脑白质疏松程度(P<0.01),减少额叶皮层区Aβ沉积(17.47±3.59 vs.4.42±1.57,P<0.01)及细胞凋亡(37.84±4.73 vs.14.42±2.43,P<0.01)。结论瑞舒伐他汀钙可改善慢性高血压大鼠的脑白质病变,减少额叶皮层区Aβ沉积以及细胞凋亡从而保护大鼠的空间记忆功能。Objective To investigate the potential effects of rosuvastatin on white matter lesion and spatial memory function in chronic hypertensive rats.MethodsFourty-nine male Sprague-Dawley rats were randomly divided into sham-operation group, vehicle-treated group, and rosuvastatin-treated group（10 mg/kg）.A model of stroke-prone renovascular hypertensive rat（RHRSP） was induced by using the two-kidney two clip method in the vehicle-treated group and the rosuvastatin-treated group. Blood pressure was monitored regularly. Morris water maze experiment was conducted to assess spatial memory function. Luxol fast blue stanning was used to examine the degree of leukoaraiosis. Immunofluorescence and electron microscopy was used to detect β-amyloid deposits. TUNEL staining was used to assess apoptosis.ResultsThe blood pressure of RHRSP increased progressively after operation.Blood pressure was significantly higher in RHRSP than in sham-operation group（P〈0.01）. The escape latencies of the rosuvastatin-treated group were markedly shorter in RHRSP than in sham-operation group（P〈0.01）. The numbers of crossing hidden platform in the 3 groups of rats were 4.55±1.23, 1.00±0.80 and 3.79±0.95 times. There were significantly differences in numbers of crossing hid-den platform among three groups（P〈0.01）. Luxol fast blue stanning showed that the grading scores for WML were lower in the rosuvastatin-treated than in the vehicle-treated group（P〈0.01）. Rosuvastatin significantly decreased the burden of Aβ deposits（17.47±3.59 vs. 4.42±1.57,P〈0.01）and the TUNEL＋cells（37.84±4.73 vs. 14.42±2.43,P〈0.01）in the frontal cortex when compared with the vehicle-treated group. Conclusions Rosuvastatin may ameliorate spatial memory function through attenuation of white matter lesion, Aβ deposits and apoptosis.

关 键 词：高血压 脑白质病 认知障碍 

分 类 号：R965[医药卫生—药理学]