法舒地尔对慢性脑缺血大鼠认知功能及皮层自由基代谢的影响.docVIP

法舒地尔对慢性脑缺血大鼠认知功能及皮层自由基代谢的影响 　　作者：王晓明 赵晴 莽靖 魏爱宣 何金婷 陈晓红 徐忠信 作者单位：吉林大学中日联谊医院神经内科，吉林 长春 130033 　　【摘要】目的 观察法舒地尔对慢性脑缺血大鼠学习记忆及皮层线粒体自由基代谢的影响。方法 大鼠分为假手术组、模型组和法舒地尔组，取3、6、9 w 3个时间点，采用双侧颈总动脉永久性阻断法(2VO)建立慢性脑缺血模型，应用Morris水迷宫检测学习记忆能力，同时检测皮层线粒体超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果 模型组和法舒地尔组大鼠与假手术组相比逃避潜伏期和游泳路径均明显延长，法舒地尔组学习记忆成绩均明显优于模型组(均P<0.05)，缺血3 w起，模型组大鼠皮层SOD活性显著降低，MDA含量明显升高，法舒地尔组与模型组SOD活性和MDA含量差异显著(均P<0.05)。结论 法舒地尔能明显减轻大鼠慢性脑缺血所致认知功能障碍，其机制可能通过清除自由基减轻神经功能损伤而改善学习记忆功能。 　　【关键词】 法舒地尔 慢性脑缺血 学习与记忆 自由基 　　Effect of fasudil on cognitive function of rats by mediating free radial metabolism in cortex and hippocampus 　　WANG XiaoMing, ZHAO Qing, MANG Jing, et al. 　　Department of Neurology, ChinaJapan Union Hospital of Jilin University, Changchun 130033, Jilin, China 　　【Abstract】 Objective To investigate the effect of fasudil on learning and memory function and free radical metabolism in cortex and hippocampus of the rats with chronic cerebral ischemia. Methods Chronic cerebral ischemia rats model was established by bilateral common carotid artery permanent blocking. The rats were divided into sham operation，ischemia model and fasudil groups. Learning and memory function of the rats were tested with Morris water maze, SOD activity and MDA content in cortex and hippocampus were measured. Results The escape latency and swim distance of model and fasudil groups were longer than those of sham operation group (P<0.05). SOD activity significantly decreased and MDA contents obviously increased in model group at 3 w, there were significant difference between fasudil group and model group (P<0.05). Conclusions Fasudil could improve learning and memory function of cerebral ischemia rats by scavenging free radical and mediating free radial metabolism in cortex and hippocampus. 　　【Key words】 Fasudil; Chronic cerebral ischemia; Learning and memory;Free radical 　　慢性脑缺血是血管性痴呆、Alzheimers病(AD)和Binswanger病等多种疾病发展过程中的一个共同病理过程。因此，目前非常重视对慢性脑缺血致认知功能障碍防治的研究。法舒地尔是Rho/Rock信号通路的选择性蛋白激酶抑制剂，在急性脑缺