阿托伐他汀对Aβ_(1-42)诱导的大鼠AD模型保护作用及其机制研究  

Protective effects of atorvastatin on Aβ_(1- 42)-induced AD model rats and its mechanism

作　　者：张玲玲[1] 金英[1] 隋海娟[1] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121001

出　　处：《中国药理学通报》2014年第2期270-274,共5页Chinese Pharmacological Bulletin

基　　金：辽宁医学院校长基金-奥鸿博泽研究生科研创新基金(No 2012005);辽宁医学院青年科技启动基金项目(No Y2012Z020)

摘　　要：目的观察阿托伐他汀(atorvastatin,Ato)对Aβ1-42诱导的AD大鼠学习记忆功能、炎症因子释放以及突触素(synaptophysin,SYP)和磷酸化JNK(p-JNK)蛋白表达的影响及机制。方法选用健康SD大鼠60只,随机分为4组:正常对照组、Aβ1-42组、Ato+Aβ1-42组、Ato组,每组15只,采用侧脑室注射给药。应用酶联免疫吸附(ELISA)法检测AD大鼠海马组织上清液内白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)含量;Morris水迷宫实验观察AD大鼠的行为学变化;Western blot法检测AD大鼠海马突触素(synaptophysin,SYP)、pJNK蛋白表达水平。结果与正常对照组相比,脑室注射Aβ1-42后大鼠出现明显的学习记忆障碍,即逃避潜伏期明显延长,原平台象限游泳时间占总游泳时间百分比明显降低(P<0.01);海马组织上清液中IL-1β、IL-6、TNF-α的含量明显增加(P<0.01);SYP蛋白表达量明显减少(P<0.01);pJNK蛋白表达水平明显增加(P<0.01)。Ato给药后可明显对抗Aβ1-42引起的大鼠学习记忆障碍,抑制Aβ1-42引起的IL-1β、IL-6、TNF-α含量(P<0.05,P<0.01)、SYP蛋白表达增加(P<0.01)及p-JNK蛋白表达水平明显减少(P<0.05)。结论 Ato能够明显改善Aβ1-42引起的AD大鼠学习记忆障碍、炎症细胞因子释放增加及SYP蛋白表达降低,这种保护作用可能与Ato抑制JNK信号转导通路的激活有关。Aim To investigate the effect of atorvasta-tin （Ato） on Aβ1_42 induced spatial learning and memory ability in AD rats and the responsible mecha-nisms. Methods Sixty healthy male Sprague-Dawley （SD） rats were randomly divided into four groups ： con-trol group, Aβ1_42 group, and Ato ＋ Aβ1_42 group, and Ato group, n = 15. The intracerebroventricular in-jection of medication was adopted. Enzyme-linked im-munosorbent assay （ELISA） was used to examine the content of interleukin-1 [3 （ IL-1β ）, and interleukin-6 （IL-6） and tumor necrosis factor-（TNF-α） , and in-terleukin-4 （IL-4） in rat hippocampus supernatant. Morris water maze experiment was applied to observe the change of behavior in AD rats. The protein expres- sions of SYP and p-JNK were determined by Western blot in rat hippoeampus. Results Injection after A[31-42 single ventricles model, compared with normal control group, the escape latency increased and per- centage of time spent in the target quadrant was low-ered （P 〈0.01 ） , the expression of hippocampus SYPsignificantly decreased （P 〈 0.01 ） and IL-1 [3, IL-6, TNF-α levels and the expression of p-JNK increased （P 〈0.01 ） in the hippocampus of AD rats. After in- traventricular injection of Ato, compared with Aβ1_42 group, Ato ＋ Aβ1_42 significantly shortened escape la- tency, increased the percentage of time spent in the target quadrant （P 〈0.05, P 〈0. 01 ） and the expres- sion of SYP （P 〈0.01）, and IL-I[3, IL-6, TNF-o~ levels and the expression of p-JNK significantly de- creased （P 〈 0.01 ） in the hippocampus of AD rats. Conclusions Ato can significantly improve the spatial learning and memory impairment of A[31-42 induced AD rats, increase the release of inflammatory cytokines and decrease SYP protein expression. These protective effects may be related to Ato inhibiting the activation of JNK signal transduction pathway.

关 键 词：阿托伐他汀 8淀粉样蛋白 炎症因子 Morris水迷 宫突触素 信号转导通路 

分 类 号：R-332[医药卫生] R322.81