Rho激酶抑制剂Fasudil对Aβ_(1-42)诱导AD模型大鼠抗氧化作用研究  

The antioxidant effect of Rho kinase inhibitor Fasudil on rat model of AD induced by Aβ_(1-42)

作　　者：宋云[1] 苏磊[2] 陈旭[2] 

机构地区：[1]山东省千佛山医院,山东济南250014 [2]山东省精神卫生中心

出　　处：《精神医学杂志》2014年第6期409-412,共4页Journal of Psychiatry

基　　金：山东省医药卫生科技发展计划项目面上项目(编号:2013WS0153)

摘　　要：目的探讨Rho激酶抑制剂Fasudil对β淀粉样蛋白1-42(Aβ1-42)诱导阿尔茨海默病大鼠学习、记忆功能和海马区氧化应激指标的影响。方法 80只成年雄性Wistar大鼠随机分成对照组(侧脑室模拟注射+生理盐水腹腔注射)、模型组(侧脑室Aβ1-42注射+生理盐水腹腔注射)、Fasudil低剂量组[侧脑室Aβ1-42注射+Fasudil 5 mg/(kg·d)腹腔注射]、Fasudil高剂量组[侧脑室Aβ1-42注射+Fasudil 10 mg/(kg·d)腹腔注射],每组各20只。采用侧脑室注射Aβ1-42制备AD模型,Fasudil腹腔注射14 d干预。Morris水迷宫实验进行大鼠的行为学测试,采用分光光度法测定海马组织匀浆中谷胱苷肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果模型组大鼠水迷宫实验的逃避潜伏期明显较对照组延长(P<0.01),目标象限活动时间和穿台次数明显少于对照组(P<0.01);海马组织匀浆中SOD、GSH-Px活性明显下降(P<0.05,P<0.01),MDA的含量增加(P<0.05)。Fasudil高剂量组逃避潜伏期明显短于模型组(P<0.01),目标象限活动时间和穿台次数明显多于模型组(P<0.01);海马组织匀浆中SOD、GSH-Px活性较模型组增加(P<0.05),MDA含量变化不明显。结论 Fasudil能够剂量依赖性的减少Aβ1-42诱导AD大鼠模型海马区的氧化应激反应,改善其学习、记忆功能。Objective To explore the antioxidant effect of Rho kinase inhibitor-Fasudil-on learning and memory function,as well as oxidative stress markers in hippocampus of rats with Alzheimer＇s disease （AD） induced by β-amyloid1-42 （Aβ1-42）.Methods 80 adult male Wistar rats were randomly divided into contro group （20 rats,lateral ventricle sham injection ＋ intraperitoneal NS injection）,AD model group （20 rats,lateral ventricle Aβ1-42 injection ＋ intraperitoneal NS injection）,low dose Fasudil group [20 rats,lateral ventricle Aβ1-42 injection ＋ intraperitoneal Fasudil 5 mg/（kg· d） injection] and high dose Fasudil group [20 rats,lateral ventricle Aβ1-42 injection ＋ intraperitoneal Fasudil 10mg/（kg·d） injection].The AD model was prepared with Aβ1-42 injection in lateral ventricle and the intervention was performed with intraperitoneal Fasudil injection.Morris water maze was used to observe the learning and memory function.Oxidative stress markers in hippocampus,which included SOD,GSH-Px and MDA,were measured by spectrophotometric method.Results Compared with the control group,rats in AD model group showed significantly longer escape latency of water maze （P 〈 0.01）,significantly shorter time spend in target and significantly less number of platform crossing （P 〈0.01）,as well as significantly decreased activity of SOD （P 〈 0.05） and GSH-Px （P 〈0.01）,significantly increased level of MDA （P 〈0.05） in hippocampus homogenate.Compared with AD model group,rats in high dose Fasudil group showed significantly shorter escape latency of water maze （P 〈 0.01）,significantly longer time spend in target and significantly more number of platform crossing （P 〈 0.01）,as well as significantly increased activity of SOD and GSH-Px （P 〈 0.05） in hippocampus homogenate.There was no significantly difference in level of MDA in hippocampus homogenate between AD model group and high dose Fasudil group.Conclusion Fasudil can eliminate the oxidative stress reaction i

关 键 词：阿尔茨海默病 RHO激酶抑制剂 FASUDIL 氧化应激 

分 类 号：R741.05[医药卫生—神经病学与精神病学]