金思维对拟散发性AD小鼠海马PSD95和Shank1表达及学习记忆的影响  

The effect of Jinsiwei on improving learning and memory in SAD mice by regulating the expressions of PSD95 and Shank1

作　　者：黄帅阳 吴艺琼 巩卓彦 王亚晗 玛娜璐璐 刘珍洪 秦高凤 王蓬文[1] HUANG Shuaiyang;WU Yiqiong;GONG Zhuoyan;WANG Yahan;MANA Lulu;LIU Zhenhong;QIN Gaofeng;WANG Pengwen(Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Key Laboratory of Beijing City,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院中医内科学教育部北京市重点实验室,100700 [2]江苏省中西医结合医院 [3]新疆医科大学中医学院中西医结合教研室

出　　处：《环球中医药》2020年第5期772-777,共6页Global Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81573927);北京市教育委员会科学研究与研究生培养共建项目(2016)。

摘　　要：目的通过研究中药复方金思维(简称金思维)对拟散发性阿尔茨海默病(sporadic Alzheimer’s disease,SAD)模型小鼠海马神经元突触相关蛋白突触后致密蛋白95(postsynaptic density95,PSD95)和骨架蛋白(Shank1)的表达,探究金思维对拟SAD小鼠学习记忆的改善作用。方法链脲佐菌素(streptozotocin,STZ)对C57/BL6J小鼠双侧侧脑室隔日注射,制备拟SAD模型;将部分小鼠双侧侧脑室注射人工脑脊液作为对照组(0.5%CMC)。随机将拟SAD模型小鼠分为模型组(0.5%CMC)、多奈哌齐组(0.92 mg·kg-1·d-1)、金思维大、中、小剂量组(20、10、5 mg·kg-1·d-1),每组12只,连续灌胃3个月。在最后一次灌胃结束后进行行为学跳台检测并取材。运用蛋白质印迹法和免疫组织化学染色技术对小鼠海马CA1区PSD95和Shank1蛋白进行检测。结果蛋白印迹法和免疫组化结果趋势一致,模型组小鼠海马CA1区PSD95表达(P<0.01)和Shank1表达(P<0.05)较于对照组均降低,且金思维各干预组较模型组不同程度增加了PSD95和Shank1蛋白的表达(P<0.01或P<0.05)。结论金思维可能通过调节突触相关蛋白PSD95和Shank1来改善突触的结构和功能,进而提高拟SAD小鼠记忆获得和保持能力。Objective To study the effect of Jinsiwei on expression of postsynaptic density95(PSD95)and skeletal protein Shank1 in hippocampal neurons of mice with sporadic Alzheimer’s disease(SAD),and to explore the improvement of learning and memory in SAD model mice.Methods The streptozotocin(STZ)were injected into bilateral lateral ventricles of C57/BL6J mice every other day,in order to established SAD model mice.Artificial cerebrospinal fluid was injected into bilateral lateral ventricles of some mice as control group(0.5%CMC).SAD model mice were randomly divided into model group(0.5%CMC),donepezil group(0.92 mg·kg-1·d-1),Jinsiwei high,medium and low dose groups(20,10 and 5 mg·kg-1·d-1),with 12 mice in each group and continuous gavage for 3 months.At the end of the last gavage,the behavior platform was detected and sampled.PSD95 and Shank1 proteins in hippocampal CA1 of mice were detected by western blot and immunohistochemical staining.Results Western-blot and immunohistochemical staining results showed the same trend.The expression of PSD95(P<0.01)and Shank1(P<0.05)in the hippocampal CA1 area of mice in the model group was lower than those in the control group,and the expression of PSD95 and Shank1 in each Jinsiwei intervention group was increased to different extent than those in the model group(P<0.01 or P<0.05).Conclusion Jinsiwei may improve the structure and function of synapses by regulating the synapse related proteins PSD95 and Shank1,thus improving the memory acquisition and retention ability of SAD mice.

关 键 词：散发性阿尔茨海默病 金思维 突触 突触后致密蛋白95 骨架蛋白Shank1 

分 类 号：R285.5[医药卫生—中药学]