反式白藜芦醇对Aβ_(25-35)诱导的阿尔茨海默病大鼠的海马神经元的保护作用  

Protective effects of trans-resveratrol on hippocampal neurons in the rats with Aβ_(25-35) induced Alzheimer's disease

作　　者：程青格[1,2] 徐平[1] 龚其海[3] 陈群[4] 史艳红[1] 

机构地区：[1]遵义医学院附属医院,贵州遵义563000 [2]濮阳市安阳地区医院神经内科,河南安阳455000 [3]遵义医学院药理学教研室,贵州遵义563000 [4]遵义市第一人民医院神经内科,贵州遵义563000

出　　处：《华西药学杂志》2014年第3期278-281,共4页West China Journal of Pharmaceutical Sciences

基　　金：贵州省科技厅社发攻关项目(黔科合SY字[2010]3074)

摘　　要：目的观察反式白藜芦醇(TR)对Aβ25-35诱导AD大鼠海马神经元的保护作用。方法将45只大鼠随机均分为假手术组、阳性对照组(多奈哌齐1 mg·kg-1)、模型组(Aβ25-35)及TR低、高剂量组(TR 10、40 mg·kg-1);Aβ25-35注射海马内后,各组ig给药,qd,连续15 d,假手术组和模型组给予同体积的生理盐水。Morris水迷宫检测大鼠学习和记忆能力;HE染色观察海马神经元损伤情况;实时PCR法定量检测海马中APP mRNA的表达;用免疫组化及Western Blot检测caspase8蛋白表达。结果与模型组比较,TR低、高剂量组在定向航行实验中,大鼠逃避潜伏期明显缩短(P<0.05),在空间搜索实验中校正潜伏期明显延长(P<0.05);TR能明显减轻海马神经元损伤;显著降低大鼠海马中APP mRNA和caspase 8蛋白的表达(P<0.05)。结论 TRes对Aβ25-35致AD大鼠海马神经元有保护作用,可能与抑制APP mRNA和caspase 8蛋白的表达有关。OBJECTIVE To investigate the protective effects of trans - resveratrol（TR） on hippocampal neurons of rats with Aβ25-35 induced Alzheimer＇ s disease（AD） , and explore its possible mechanisms. METHODS Rats are randomly divided into sham, positive control （donepezil） , model（Aβ25-35 ） , low and high dose TR groups, respectively. After rejection of Aβ25-35 into hippocampus, rats were administrated with 1.0 mg·kg^-1 donepezil and 10 and 40 mg.kg^-1 TR once daily by gavage for consecutive 15 days respectively,while sham and model groups were administrated with volume - matched normal saline by gavage. The learning and memory ability of rats were detected by Morris water maze test. Neuronal injury in hippocampus was observed by hematoty -eosin staining, and the mRNA levels of APP were detected by real time PCR and the protein expressions of caspase 8 were examined by immunohistochemistry and Western Blot in the rat hippocampus. RESULTS Compared with the model rats, TRes - treated groups significantly shortened the mean escape latency in the navigation test and prolonged the adjusted escape latency in spatial probe test,attenuated neuronal injury in hippocampus, and significantly decreased the mRNA expressions of APP and the proteins of caspase 8 in rat hippocampus. CONCLUSION TR has protective effect of on hippocampal neurons of rats with Aβ25-35 induced AD,its mechanisms may be at least partly due to decreasing the mRNA expressions of APP and protein expression of caspase 8 in rat hippocampus.

关 键 词：反式白藜芦醇 海马 学习 记忆 APP CASPASE8 B淀粉样蛋白前体蛋白水解产物 

分 类 号：R96[医药卫生—药理学]