2,4-二甲基反式芪改善侧脑室注射Aβ_(25-35)诱导的高脂大鼠学习记忆功能

Tran-2,4-dimethoxystibene (S3) promoted the learning and memory in model rats induced by hypercholesterolemic with i.c.v. injection of Aβ_(25-35)

目的研究2,4-二甲基反式芪(S3)对侧脑室注射Aβ25-35引起的高脂大鼠学习记忆功能障碍的作用及初步机制。方法雌性Wistar大鼠70只,分为正常对照组,单纯高脂组,高脂+脑室注射组和阳性药E2组[1 mg/(kg.d)];S3高、中及S3低剂量组[50、25及12.5 mg/(kg.d)]。除对照组10只大鼠外,其他组大鼠给予高脂饮食6周,测定血脂,然后给予侧脑室注射Aβ25-35,同时连续给药7天,从第3天起行Morris水迷宫及跳台实验,每天1次,连续4次,测定各组大鼠学习记忆功能;以分光光度法测定ChAT和AchE,ELISA法测定Ach浓度。结果 S3能够剂量依赖的降低侧脑室注射高脂大鼠血浆总胆固醇和LDL-C浓度(P<0.01)。高剂量组S3能够明显缩短找到平台时间、延长潜伏期并减少错误次数。同时,S3能增加海马组织ChAT活性和Ach浓度,降低AchE活性。结论 S3可能通过降低血脂浓度、增加ChAT活性、降低AchE活性而增加海马Ach浓度,从而改善模型大鼠的学习记忆功能。

Objective To investigate the effect of S3 on learning capacity and memory in rat model induced by hy- percholesterolemic with i. e. v. injection of Aβ225-35. Methods Seventy female Wistar rats were divided into 7 groups. Except the normal group, other 60 rats were fed with hypercholemic chow for six weeks, and then received an intracerebroventricular injection for once. The E2 and S3-treatment groups＇ rats were treated with E2 or S3 for an- other 7 days. Behavioral changes were evaluated by Morris water maze and step-down test. The activities of choline acetyl transferase （CHAT） and acetylcholine esterase （Ach E） were analyzed by spectrophotometric method, and the content of acetylcholine was measured by ELISA. Results S3 dose-dependently decreased serum total and LDL-C levels （ P 〈 0. 01 ） in model rats with hypercholesterolemic plus i. v. dose of S 3 shortened the escape latency significantly. The step - down latency of S 3 treated groups was restored tonear that of the control group and the number of errors was markedly reduced. Meanwhile, S3 revised the decreased activity of ChAT as well as the increased activity of Ach E in hippocampus. Conclusions S3 improved the model rats＇ learning capacity and memory by decreasing the serum cholesterol, increasing the concentration of Ach in hip- pocampus through changes of ChAT and Ach E activities.