法舒地尔对慢性低灌注大鼠认知功能、Rho激酶表达及海马一氧化氮合酶阳性神经元的影响  

The Effects of a Rho Kinase Inhibitor on Cognitive Function and Nitric Oxide Synthase Positive Neurons in Hippocampus of Rats with Chronic Hypoperfusion Status

作　　者：林琅[1,2] 张微微[1] 黄勇华[1] 郭文华[1] 赵秀欣[1] 

机构地区：[1]北京军区总医院神经内科,北京100700 [2]第三军医大学,重庆400038

出　　处：《神经损伤与功能重建》2009年第4期241-243,256,共4页Neural Injury and Functional Reconstruction

摘　　要：目的:探讨Rho激酶抑制剂法舒地尔对慢性低灌注大鼠认知功能损害的影响及其可能机制。方法:60只雄性Wistar大鼠随机分为假手术组、缺血组、法舒地尔组各20只,缺血组及法舒地尔组结扎双侧颈总动脉,而假手术组不结扎;术后假手术组和缺血组每日腹腔注射生理盐水1mL,法舒地尔组每日腹腔注射法舒地尔2mg/kg。于术后第23天开始对大鼠进行为期5d的水迷宫适应训练,术后第28、29天评测大鼠认知功能,术后第30天将大鼠处死取脑,采用RT-PCR测定Rho激酶mRNA表达水平,并采用组织化学染色观察海马一氧化氮合酶(NOS)阳性神经元的形态和数目。结果:与假手术组比较,缺血组大鼠认知功能显著降低,Rho激酶mRNA表达水平明显增高,海马NOS阳性神经元数目增多且染色较深;与缺血组比较,法舒地尔组大鼠认知功能改善,海马NOS阳性神经元数目减少且染色变浅,但Rho激酶mRNA表达水平无明显差异。结论:慢性低灌注大鼠认知功能明显降低,Rho激酶异常活化与一氧化氮产生增多可能参与其作用机制;Rho激酶抑制剂法舒地尔可改善慢性低灌注大鼠的认知损害,其作用机制并非调控Rho激酶的基因表达,可能与改善脑血流、抗过氧化应激作用有关。Objective：To determine the role of Rho kinase in cognitive function induced by chronic hypoperfusion.. Methods：Sixty male Wistar rats were divided into the control, ischemic and fasudil treatment groups. The rats in both the ischemic and fasudil treatment groups have received bilateral carotid artery ligation, and the rats in the fasudil treatment group received daily intraperitoneal injection of fasudil, an inhibitor of Rho kinase. Morris wa- ter maze test, RT-PCR for Rho kinase mRNA and immunohistochemistry for nitric oxide synthase positive neurons were performed at day 30 after the operation. Results：In comparison with the control group, the rats in the ischemic group showed lower performance on Morris water maze test, upregulated expression of Rho kinase mRNA and in- creased numbers of nitric oxide synthase positive neurons in hippocampus. When compared with the ischemic group, the rats in the fasudil treatment group demonstrated improved performance on Morris water maze test and decreased numbers of nitric oxide synthase positive neurons in hippocampus. Conclusion ： Abnormally activated Rho kinase may be involved in the chronic hypoperfusion, and leads to cognitive impairment by increasing the production of nitric oxide. Treatment with Rho kinase inhibitors could attenuate the cognitive impairment induced by chronic hypoperfusion.

关 键 词：认知障碍 RHO激酶 一氧化氮合酶 低灌注 

分 类 号：R741[医药卫生—神经病学与精神病学] R749.1[医药卫生—临床医学]