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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。
Objective To investigate the effects of atorvastatin on learning and memory, release of inflammatory cytokines and the expression of synaptophysin (SYP) and phosphorylated JNK (p-JNK) induced by Aβ 1-42 in AD rats. mechanism. Methods Sixty healthy SD rats were randomly divided into 4 groups: normal control group, Aβ1-42 group, Ato + Aβ1-42 group, Ato group, 15 rats in each group. The levels of IL-1β, IL-6 and TNF-α in the hippocampus of AD rats were detected by enzyme linked immunosorbent assay (ELISA) ), Interleukin-4 (IL-4) were measured. Morris water maze test was used to observe the changes of behavior in AD rats. Western blot was used to detect the protein expression of synaptophysin (SYP) and pJNK in hippocampus of AD rats. Results Compared with the normal control group, there was a significant learning and memory impairment in rats after Aβ 1-42 injection. That is to say, the escape latency was significantly prolonged. The swimming time in the original platform quadrant was significantly lower than that in the total swimming time (P <0.01) The levels of IL-1β, IL-6 and TNF-α in the supernatant were significantly increased (P <0.01). The expression of SYP protein was significantly decreased (P <0.01) and the protein expression of pJNK was significantly increased (P <0.01). Ato could obviously antagonize the learning and memory impairment induced by Aβ1-42, inhibit the levels of IL-1β, IL-6 and TNF-α induced by Aβ1-42 (P <0.05, P <0.01) (P <0.01) and p-JNK protein expression decreased significantly (P <0.05). Conclusions Ato can significantly improve the learning and memory impairment, the increase of inflammatory cytokines and the decrease of SYP protein expression in AD rats induced by Aβ1-42. This protective effect may be related to the inhibition of Ato on the activation of JNK signal transduction pathway.