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.
出处
《中国药理学通报》
CAS
CSCD
北大核心
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)
