红景天苷对阿尔茨海默病模型大鼠学习记忆能力和海马组织Aβ含量及p75NTR表达的影响

摘要

Objective To study the effect of salidroside (Sal) on learning and memory abilities and expression of p75NTR signal transducers and Aβ in AD rat hippocampus.Methods Totally,ninety-six male SD rats were randomly divided into sham-operation group,model control group,Sal low,medium and high dose group,Hup-A group (16 rats in each group).Except for sham-operation group,AD model in the other group was established by slowly injecting 1μL(10 μg)Aβ1-40 in tobilateral hippocampal CA1 area.Sham-operation group was given the same volume of 0.9％ sodium chloride solution.Sal low,medium and high dose group took orally as early as 24 h postoperatively with salidroside 25,50,100 mg· kg-1 for 21days,while Hup-A group took 50 mg kg-1 of Hup-A orally.The same volume of 0.9％ sodium chloride solution was administrated in shanmoperation group and model control group.After administration,the learning and memory function of rats were tested by Morris water maze.The contents of Aβ in serum and hippacampus were determined by ELISA,and protein expression of p75NTR and p-JNK in the hippocampus of the rats were measured by ELISA.Results Compared with model control group,the latent time in water maze training of Sal low,medium and high dose groups were significantly shortened (P ＜ 0.05 or P ＜ 0.01),the number of times of crossing platform of Sal low,medium and high dose group was significantly increased.The contents of Aβ in the hippocampus and the protein expression levels of p75NTR and p-JNK in the hippocampus of Sal low,medium and high dose group were decreased significantly (P ＜ 0.05,P ＜ 0.01).Conclusion Salidroside has protective effects on learning and memory consolidation of dysmnesia rats caused by Aβ.Its mechanism might be related to inhibition of p75NTR regulation pathways for Aβ,reducing the neurotoxic effect of Aβ,so as to reduce cell apoptosis of hippocampus neuron.%目的 探讨红景天苷对Aβ1～40所致阿尔茨海默病(AD)模型大鼠学习记忆能力,p75NTR信号通路关键蛋白表达和β-淀粉样蛋白(Aβ)含量的影响.方法选取96只雄性SD大鼠,随机分为假手术组,模型对照组,红景天苷小、中、大剂量组,石杉碱甲组,每组16只.除假手术组外,各组大鼠均于双侧海马CA1区缓慢注射Aβ1～40各1μL(10μg)制备AD大鼠模型,假手术组则注射等量0.9％氯化钠溶液.红景天苷小、中、大剂量组分别于术后24h灌胃红景天苷25,50,100 mg·kg-1,石杉碱甲组给予灌胃石杉碱甲50 mg· kg-,假手术组及模型对照组灌胃等量0.9％氯化钠溶液,共21 d.给药结束后经Morris水迷宫实验观察红景天苷对模型大鼠学习记忆能力的影响,并采用酶联免疫吸附测定(ELISA)法检测大鼠血清与海马组织中Aβ的含量,免疫组化法检测海马区神经元中p75NTR和p-JNK蛋白表达.结果 与模型对照组比较,红景天苷小、中、大剂量组大鼠在水迷宫训练中潜伏期明显缩短(P ＜0.05或P＜0.01),而水迷宫测试中跨越平台的次数显著增加(P ＜0.05或P＜0.01);红景天苷小、中、大剂量组血清与海马组织中Aβ含量显著降低;海马神经元p75NTR、p-JNK表达显著减少(P＜0.05或P＜0.01).结论 红景天苷可改善Aβ1-40所致学习记忆障碍模型大鼠学习记忆能力,其作用机制可能与其抑制p75NTR对Aβ的调控通路,减少Aβ的神经毒性作用,从而使海马神经细胞凋亡减少有关.