吡格列酮对慢性高血压大鼠脑白质病变和空间记忆功能的影响  

Effect of pioglitazone on white matter lesions and spatial memory function in chronic hypertensive rats

作　　者：蓝琳芳[1] 范玉华[1] 郑璐[1] 杨娴[2] 

机构地区：[1] 中山大学附属第一医院神经科, 广州510080 [2] 福建省立医院内科, 福州350001

出　　处：《国际脑血管病杂志》2013年第12期892-897,共6页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学青年基金（81000514）;广东省自然科学基金（S2013010015840）

摘　　要：目的 探讨过氧化物酶体增殖物激活受体γ激动剂吡格列酮对慢性高血压大鼠脑白质病变和空间记忆功能的影响.方法 雄性Sprague-Dawley大鼠36只,随机分为假手术组（n=6）、高血压组（n=15）和吡格列酮组（n=15）.高血压组和吡格列酮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,术后8周开始灌胃给药.吡格列酮组给予10 mg/（kg＆#183;d）吡格列酮,高血压组给予等量生理盐水,分别于术前、给药前及给药后每隔2周经尾动脉监测血压.连续给药12周后进行Loyez染色观察脑白质疏松程度,水迷宫试验检测空间记忆功能.结果 RHRSP大鼠造模后血压缓慢升高,显著性高于假手术组（P均=0.000）,高血压组与吡格列酮组血压无显著性差异（P =0.897）.水迷宫试验显示,假手术组和吡格列酮组逃避潜伏期显著性短于高血压组（P均＜0.05）,三组大鼠跨越平台次数分别为（5.200＆#177;1.798）次、（4.560＆#177;1.592）次和（2.333＆#177;1.978）次,差异具有统计学意义（F=8.143,P=0.001）,假手术组和吡格列酮组均显著性多于高血压组（P均＜0.05）.Loyez染色显示,假手术组、高血压组和吡格列酮组胼胝体脑白质病变分级分别为0.333＆#177;0.516、2.600＆#177;0.507和0.500＆#177;0.522,三组间差异有统计学意义（F =25.652,P=0.000）,假手术组和吡格列酮组分级均显著性低于高血压组（P均＜0.05）.结论 PPAR-γ激动剂吡格列酮能通过减轻慢性高血压大鼠脑白质病变保护空间记忆功能.Objective To investigate the effect of peroxisome proliferator-activated receptor γ （PPARγ） agonist pioglitazone on white matter lesions and spatial memory function in chronic hypertensive rats.Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group （n =6）,a hypertensive group,（n =15）,and a pinglitazone group （n =15）.A model of stroke-prone renovascular hypertensive rat （RHRSP） was induced by the two-kidney two clip method in the hypertensive group and pioglitazone group.At 8 weeks after procedure,the rats were administered intragastrically.10 mg/（kg ＆#183; d） pioglitazone was given in the pioglitazone group and an equal volume of saline was given in the hypertensive group.Blood pressure was monitored via caudal artery every 2 weeks before procedure,before administration,and after administration,respectively.After 12 weeks of continuous administration,Loyez staining was used to observe the degree of leukoaraiosis,and Morris water maze test was used to detect spatial memory function.Results After modeling,the blood pressure of RHRSP increased gradually.It was significantly higher than the sham operation group （all P =0.001）.There was no significant difference in blood pressure between the hypertensive group and the pioglitazone group （P =0.897）.The Morris water maze test showed that escape latencies of the sham operation group and the pioglitazone group were significantly shorter than the hypertensive group （all P 〈0.05）.The numbers of crossing hidden platform in the 3 groups of rats were 5.200 ＆#177; 1.798,4.560 ＆#177; 1.592,and 2.333 ＆#177; 1.978 times,respectively.There were significantly differences （F =8.143,P =0.001）.Both the sham operation group and the pioglitazone group were significantly more than the hypertensive group （all P 〈0.05）.Loyez staining showed that the grades of white matter lesions in corpus callosum of the sham operation group,the hypertensive group,and the pioglitazone group were 0.333 ＆#177;

关 键 词：噻唑烷二酮类 吡格列酮 过氧化物酶体增生物激活受体Γ 高血压 脑白质病 认知障碍 大鼠 PPARγ 

分 类 号：R544.1[医药卫生—心血管疾病]