淫羊藿次苷Ⅱ调节海马tau蛋白磷酸化水平改善慢性脑低灌注大鼠的学习记忆功能障碍

Icariside Ⅱ Improves Learning and Memory Impairments Induced by Chronic Cerebral Hypoperfusion Through Regulating Tau Phosphorylation Levels in Rat Hippocampus

目的:研究淫羊藿次苷Ⅱ(ICSⅡ)抗慢性脑低灌注(CCH)诱导的大鼠学习记忆功能减退的作用及其可能的作用机制。方法:Morris水迷宫实验检测大鼠学习记忆能力,HE染色观察海马神经元的形态,Nissl染色观察海马神经元的存活数量,Western blot检测海马tau蛋白在丝氨酸199位点磷酸化(p-Ser 199-tau)、丝氨酸396位点磷酸化(p-Ser 396-tau)、丝氨酸404位点磷酸化(p-Ser 404-tau)及苏氨酸231位点磷酸化(p-Thr 231-tau)的水平。结果:ICSⅡ(16 mg/kg)能改善CCH大鼠的学习记忆障碍,减轻海马CA1区神经元结构损伤,增加海马CA1区存活神经元数量,降低海马p-Ser 199-tau、p-Ser 396-tau、p-Ser 404-tau、p-Thr 231-tau的水平。结论:ICSⅡ具有改善CCH所致大鼠学习记忆功能减退及海马神经元损伤的作用,其机制可能与下调tau蛋白异常磷酸化水平有关。

Objective To investigate the effect of icariside Ⅱ(ICS Ⅱ) on learning and memory impairments induced by chronic cerebral hypoperfusion(CCH)and the possible mechanisms in rats.Methods The learning and memory function of rats were detected by Morris water maze;morphology of hippocampal neurons were detected by HE staining;Neuronal survival quantity of hippocampus were detected by Nissl staining;Western blot was used to examine the levels of p-Ser199-tau,p-Ser396-tau,p-Ser404-tau and p-Thr231-tau.Results ICS Ⅱ(16 mg/kg) could improve learning and memory induced by CCH in rats,attenuate the hippocampal CA1 region neurons injury,increase the number of surviving neurons in hippocampal CA1 region,and decrease the levels of p-Ser 199-tau,p-Ser 396-tau,p-Ser 404-tau,p-Thr 231-tau in hippocampus.Conclusion Icariside Ⅱ has an improvement effect on CCH-induced learning and memory impairments and neuronal injury of hippocampus in rats.The mechanism may be related to the down-regulation of tau phosphorylation levels.