电针对阿尔茨海默病大鼠学习记忆能力及前额叶P35/P25-周期蛋白依赖性激酶5-Tau蛋白磷酸化通路的影响  

Effects of Electroacupuncture on Learning-memory and P35/P25-Cyclin-dependent Kinase 5-Tau Phosphorylation Signal Pathway in Prefrontal Cortex of Rats with Alzheimer's Disease

作　　者：王依滢 唐成林[2] 邱国平[1] 徐进[1] 隆令 许毅[3] 王健蓉[4] 甘胜伟[1] 盛华均[1] 朱淑娟[1] WANG Yi-ying;TANG Cheng-lin;QIU Guo-ping;XU Jin;LONG Ling;XU Yi;WANG Jian-rong;GAN Sheng-wei;SHENG Hua-jun;ZHU Shu-juan(The Department of Human Anatomy,Chongqing Medical University,Chongqing 400016,China;College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400016,China;College of Medicine,Chengdu University,Chengdu,Sichuan 610106,China;Department of Neurology,the Fifth People's Hospital of Chengdu,Chengdu,Sichuan 611130,China)

机构地区：[1]重庆医科大学人体解剖教研室,重庆市400016 [2]重庆医科大学中医药学院,重庆市400016 [3]成都大学医学院,四川成都市610106 [4]成都市第五人民医院神经内科,四川成都市611130

出　　处：《中国康复理论与实践》2020年第6期654-661,共8页Chinese Journal of Rehabilitation Theory and Practice

基　　金：国家自然科学基金面上项目(No.81273870);重庆市市科委项目(No.cstc2017jcyjAX0414,No.cstc2016jcyjA0229,No.cstc2016jcyjA0073);重庆市教委项目(No.KJ1600213)。

摘　　要：目的观察电针百会、肾俞两穴对阿尔茨海默病(AD)模型大鼠学习记忆能力及前额叶皮质(PFC)P35/P25-周期蛋白依赖性激酶5(CDK5)-Tau蛋白磷酸化信号通路的影响,以探讨电针治疗AD的相关机制。方法雄性成年Sprague-Dawley大鼠随机分为正常对照组、假手术组、模型组和电针组,每组6只。后两组双侧海马注射Aβ25-35,假手术组注射等量生理盐水。造模后次日,电针组电针百会、肾俞,留针15 min,每天1次,共10 d。治疗后,行Morris水迷宫实验,免疫组织化学染色和Western blotting检测各组PFC P35/P25-CDK5-Tau蛋白磷酸化相关蛋白的表达情况。结果与正常对照组和假手术组比较,模型组的逃避潜伏期和搜索路径均增加(P<0.05),穿越平台次数减少(P<0.05);与模型组比较,电针组逃避潜伏期和搜索路径均缩短(P<0.05),穿越平台次数增加(P<0.05)。模型组P35/P25和CDK5阳性表达明显高于正常对照组和假手术组(P<0.01),电针组显著低于模型组(P<0.001)。模型组P35/P25、CDK5、Tau[pS199]、Tau[pS202]相对表达量高于正常对照组和假手术组(P<0.05),电针组上述蛋白的表达低于模型组(P<0.05)。结论电针刺激能有效改善AD大鼠的学习记忆和空间探索能力,可能通过影响大鼠PFC的P35/P25-CDK5-Tau蛋白磷酸化信号通路,延缓AD的发生与发展。Objective To observe the effect of electroacupuncture at Baihui(DU20)and Shenshu(BL23)acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5(CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex(PFC)in rats with Alzheimer's disease(AD),so as to reveal its potential mechanisms in treating AD.Methods Male adult Sprague-Dawley rats were randomly divided into normal control group,sham group,model group and treatment group with six rats in each group.The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups.Equal amount of normal saline was injected into the sham group.The treatment group was acupunctured at Baihui and Shenshu once a day for ten days.All the rats were tested with Morris Water Maze.Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC.Results Compared with the normal control group and the sham group,the escape latency and escape length increased(P<0.05)and the times crossing the platform reduced(P<0.05)in the model group;compared with the model group,the escape latency and escape length reduced(P<0.05),and the times crossing the platform increased(P<0.05)in the treatment group.The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group(P<0.01),and they were lower in the treatment group than in the model group(P<0.001).The relative expression of P35/P25,CDK5,Tau[pS199]and Tau[pS202]were higher in the model group than in the normal control group and the sham group(P<0.05),and the expression of the above proteins was lower in the treatment group than in the model group(P<0.05).Conclusion Electroacupuncture could improve the learning-memory and spatial exploration ability,which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.

关 键 词：阿尔茨海默病 电针 前额叶皮质 P35/P25-周期蛋白依赖性激酶5-Tau蛋白磷酸化 大鼠 

分 类 号：R749.1[医药卫生—神经病学与精神病学]