蜕皮甾酮改善Aβ25-35大鼠学习记忆功能障碍与ChAT相对高表达有关

目的探讨蜕皮甾酮(Ecdysterone,ECR)改善Aβ25-35诱导大鼠学习记忆功能障碍的作用机制。方法Wistar大鼠90只(♂)随机分为5组:对照组(control),模型组(Aβ),三个治疗组ECR4mg.kg-1(Aβ ECR4),ECR8mg.kg-1(Aβ ECR8),Nimodipine7.2mg.kg-1(Aβ -Ni7.2)],每组18只。大鼠双侧海马内注射Aβ25-35(每侧5μl,2μg.μl-1)诱导学习记忆功能障碍;水迷宫检测Aβ25-35诱导的大鼠学习记忆行为学改变;免疫组化SP法检测ChAT表达情况;AchE活性由试剂盒检测。结果①行为学的水迷宫检测结果显示,在连续4天的获得实验期间,与对照组比较,模型组找到平台的潜伏期和搜索距离明显增加(P<0.01);与模型组比较,高剂量ECR组及尼莫地平组大鼠找到平台的潜伏期和搜索距离相对缩短(ECR8mg.kg-1,P<0.01;-Ni7.2mg.kg-1,P<0.05)。在第5天撤去平台的记忆测试中:与对照组比较,模型组在原平台区的搜索时间及距离均缩短(P<0.01),而治疗组平台区的搜索时间及距离则相对增加(ECR4mg.kg-1P<0.05;ECR8mg.kg-1,P<0.01;Ni7.2mg.kg-1,P<0.05)。②胆碱乙酰转移酶(cholineacetyltransferase,ChAT)的分析结果显示,与对照组比较,模型组大鼠皮层及海马脑组织中的ChAT活性均明显降低(bothP<0.01);与模型组比较,高剂量ECR组及尼莫地平组大鼠皮层脑组织中ChAT活性均相对增加(ECR8mg.kg-1,P<0.01;Ni7.2mg.kg-1,P<0.05),而海马组织中只有高剂量ECR组的ChAT活性相对增加(ECR8mg.kg-1,P<0.05)。③胆碱脂酶(Acetylcholinesterase,AchE)的检测结果显示,各组大鼠的AchE活性无明显差别。结论ECR改善Aβ25-35大鼠学习记忆功能障碍,至少与皮层及海马脑组织中ChAT活性相对增加有关。

The effect of ECR on the learning and memory dysfunction of the rats induced by Aβ25-35 involved in ChAT activity

Objective To explore the mechanism of ecdysterone (ECR) in prevention of learning and memory dysfunction of the rats induced by β-amyloid peptide (Aβ25-35). Methods Ninety Mistar male rats were randomly divided into five groups,the control group, the model group, the treated groups ( ECR 4mg·kg-1 and ECR 8mg· kg-1 and Nimodipine 7.2mg· kg-1),18 in each group. Microinjection of Aβ25-35 (5μl,2μg· μl-1)into both hippocampi of the rats to induce a learning and memory dysfunction. Morris Water Maze test was used to evaluate the learning and memory impairment of the rats induced by Aβ25-35- The activity of ChAT was assayed by immunohistochemistry SP method. The activity of AchE was measured by the AchE kits from Nanjing Jiancheng. Results ① The results of Water Maze test showed that, during consecutive 4-day acquisition trials, rats in the model group took longer latency and searching distance than that in the control group on second, third and fourth day (P＜0.01), while the ones in the treated group took shorter latency and searching distance than that in the model group ( ECR 8mg· kg-1, Nimodipine 7.2mg· kg-1, both P＜0.05); In spatial probe trial on fifth day, the ones in the model group took shorter searching time and distance compared with that in the control group (P＜0.01), while ones in the treated group took longer searching time and distance compared with that in the model group (ECR 4mg·kg-1 P＜0.05; 8mg·kg-1, P＜0.01; Nimodipine 7.2mg·kg-1, P＜0.05). ②The level of ChAT activity were decreased from the cerebral cortices and the hippocampus of the model group compared with that in the control group (both P＜0.01). The level of ChAT activity were significantly increased in the treated groups (ECR 8mg·kg-1, P＜0.01, Nimodipine 7.2mg·kg-1, P＜0.05 ) from the cerebral cortices. Furthermore, The level of ChAT activity were increased in the treated groups (ECR 8mg·kg-1, P＜0.05 ) from the hippocampus. ③The results of AchE activity showed that, there are no significant difference among all groups both in the cerebral cortice and the hippocampus. Conclusions The ECR could improve the learning and memory dysfunction of the rats induced by Aβ25-35, and its protective mechanisms maybe related to its inhibiting the decrease of the level of ChAT activity induced by Aβ25-35.