【作者】 黄琳； 郭莲军； 李玉珍；

【Author】 Lin Huang1,Lian-jun Guo2.Li Yu-zhen1 1 Department of Pharmacy,Peking University People’s Hospital,Beijing,100044,P.R.China.2 Department of Pharmacology,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,P.R.China

【机构】 北京大学人民医院； 华中科技大学同济医学院基础医学院药理学系；

【摘要】 目的探讨Rho激酶抑制剂盐酸法舒地尔对大鼠慢性低灌性脑缺血损伤的影响。方法永久性结扎大鼠双侧颈总动脉制作大鼠慢性低灌性脑缺血损伤模型。运用Morris水迷宫检测各组大鼠空间学习记忆能力;运用在体电生理技术记录各组大鼠海马CA3区群峰电位,给予高频刺激后观察诱发长时程增强(Long-Time Potentiation,LTP)的情况;免疫组化、Western blot技术分析nNOS的表达。结果Morris水迷宫检测发现模型组大鼠学习记忆能力受损,与假手术组比较逃避潜伏期延长、空间辨别能力下降;在体电生理记录中模型组大鼠LTP诱发困难;模型组大鼠皮层和海马部位nNOS表达均减少。给予盐酸法舒地尔能改善脑缺血所致的大鼠学习记忆障碍,提高LTP诱导率和幅值,增加nNOS的表达。结论盐酸法舒地尔可以改善慢性低灌性脑缺血所致的学习记忆能力损害、突触传递功能障碍和神经元损伤,其可能的作用机制为增加nNOS的表达。更多还原

【Abstract】 OBJECTIVE:To study the effects of hydroxyl fasudil,a Rho-kinase inhibitor,on chronic cerebral hypoperfusion induced deficits in rats.METHODS:Chronic cerebral hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries.Morris water maze was used to measure spatial memory performance.Electrophysiological equipments were used to record long-term potentiation(LTP).The expression of nNOS was assayed by immunohistochemistry and Western blot.RESULTS:Chronic cerebral hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant.These behavioral dysfunctions were accompanied with reduction of LTP,decreases in nNOS protein expression.Long-term administration of hydroxyl fasudil markedly improved the spatial memory impairment,prevented the reduction of LTP,attenuated neuronal damage,enhanced the expression of nNOS.CONCLUSION:Long-term hydroxyl fasudil treatment provides neuroprotective effects on memory deficit and neuronal damage after ischemia,which may associated with enhancement of nNOS expression.Moreover,rho kinase plays a critical role in the pathogenesis of chronic ischemic cerebral damage.更多还原