卒中后抑郁大鼠PSD-95表达调控与认知功能障碍关系的研究

Study on the relationship between PSD-95 expression and cognitive impairment in the hippocampus of poststroke depression rats

目的 探讨卒中后抑郁大鼠突触后致密蛋白-95(PSD-95)表达调控与认知功能损伤的关系。方法 筛选50只行为学评分均一的大鼠,随机分为4组,正常组、卒中组、抑郁组、卒中后抑郁组,每组最终达到6只以上。采用线栓法制备大脑中动脉阻塞模型(MCAO),在此基础上综合孤养、慢性不可预见的温和应激(CUMS)复合制备卒中后抑郁大鼠模型。运用被动躲避实验评定大鼠的学习记忆能力,采用荧光定量PCR技术和免疫组织化学技术检测大鼠海马PSD-95基因和蛋白的表达变化。结果 造模成功后(术后36天),与正常组比较,抑郁组与卒中后抑郁组大鼠体重、糖水消耗量、OFT水平、PSD-95蛋白及mRNA表达水平均减少,被动规避缺陷,差异均有统计学意义(均P<0.05)。结论 卒中后抑郁大鼠海马区PSD-95表达下降可导致认知功能障碍。

Objective To make clear the relationship between postsynaptic density protein(PSD)-95 expression and cognitive impairment in post-stroke depression rats and explore the mechanism in the process of cognitive impairment.Methods 50 rats with uniform behavioral scores were randomly divided into 4 groups:normal group,stroke group,depression group,and post-stroke depression group(n≧ 6).The model of middle cerebral artery occlusion(MCAO)was established by the suture-occluded method,and the post-stroke depression rat model was established by chronic unpredictable mild stress(CUMS)combined with solitary feeding.The learning and memory ability of rats were evaluated by passive avoidance test.Real Time-PCR and immunohistochemistry method were used to detect the PSD-95 mRNA and PSD-95 protein in the hippocampus.Results After modeling successfully(36 days after operation),compared with the normal group,the depression group and the post-stroke depression group had significant changes:weight loss,the decrease of glucose consumption,the drop of open-field horizontal behavior and vertical behavior,the deficiency of passive avoidance test,the reduction of the expression of PSD-95 protein and mRNA(P<0.05).Conclusion The decrease of PSD-95 expression in the hippocampus of post-stroke depression rats may lead to cognitive impairment.