法舒地尔治疗颈动脉狭窄大鼠认知功能障碍的实验研究  

Experimental study of fasudil on cognitive impairment in rats with severe carotid stenosis

作　　者：张强[1,2] 冉昌丽[1,2] 李耀彩[1,2] 

机构地区：[1]三峡大学第一临床医学院 [2]宜昌市中心人民医院神经内科,湖北宜昌443003

出　　处：《中国新药与临床杂志》2011年第1期47-50,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的观察Rho激酶抑制药法舒地尔对重度颈动脉狭窄所致的大鼠认知功能障碍的治疗作用方法成年雄性SD大鼠36只,分为模型组、假手术组和治疗组,每组1 2只。模型组和治疗组采用"针控线拴法"制作大鼠重度颈动脉狭窄模型,假手术组仅游离双侧颈总动脉。术后2 wk治疗组腹腔注射法舒地尔8.35 mg·kg,模型组、假手术组注射生理盐水,2次·d^(-1)。给药2 wk后,Morris水迷宫检测各组大鼠的认知功能,并观察大鼠海马神经元形态的变化。结果与假手术组比较,模型组的颈总动脉狭窄率明显增加,平均逃避潜伏期明显延长,平台象限游泳距离显著下降(均P<0.01)。治疗组大鼠颈动脉狭窄率与模型组比较无明显差异[(93.20±2.21)%vs.(98.24±2.67)%,P>0.05];与模型组相应时间点比较,治疗组大鼠平均逃避潜伏期均显著缩短(P<0.01),平台象限游泳距离百分比显著增加[(46.7±3.7)%vs.(30.3±2.5)%,p<0.01],治疗组大鼠海马区神经元有明显改善。结论法舒地尔可以明显改善重度颈动脉狭窄导致的大鼠认知功能障碍。AIM To study the effect of Rho kinase inhibitor fasudil on rats with cognitive dysfunction caused by severe carotid artery stenosis.METHODS Thirty-six adult male SD rats were divided into model group,sham operation group,and treatment group,with 12 in each group.The model group and treatment group were made into the model of severe carotid artery stenosis by＂needle control line tied law＂,and the sham operation group only dissociated the bilateral common carotid artery.Two weeks later,the treatment group was ip fasudil 8.35 mg·kg^（-1） and the model group were injected with normal saline twice a day.Two weeks after the administration,Morris water maze tests were done to test cognitive function and the morphological changes of hippocampal neurons were observed.RESULTS Compared with the sham operation group,the carotid artery stenosis rate was significantly increased,the average escape latency was significantly longer,and the platform quadrant swimming distance decreased significantly in the model group（P0.01）.There was no significant decrease in stenosis rate between the treatment group and the model group（（93.20±2.21）%vs.（98.24±2.67）%,P0.05）.Compared with the model group at corresponding time point,the average escape latencies were all significantly shortened（P0.01） and the platform quadrant swimming distance increased significantly （（46.7±3.7）%vs.（30.3±2.5）%,P0.01） in the treatment group.At the same time,the neurons in hippocampus of the treatment group was significantly improved compared with that of the model group. CONCLUSION Fasudil can significantly improve cognitive impairment caused by severe carotid artery stenosis in rats.

关 键 词：法舒地尔 认知障碍 颈动脉狭窄 大鼠 

分 类 号：R965[医药卫生—药理学]