梓醇-川芎嗪方对阿尔茨海默病模型小鼠的作用及对水通道蛋白4表达的影响  

Effects of Catalpol-tetramethylpyrazine Prescription on Alzheimer′s Disease Model Mice and the Expression of Aquaporin-4

作　　者：邓楚珺 孟胜喜[1] 陈慧泽 王兵[1] 郭起浩 付剑亮[1] DENG Chujun;MENG Shengxi;CHEN Huize;WANG Bing;GUO Qihao;FU Jianliang(Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China)

机构地区：[1]上海交通大学医学院附属第六人民医院,上海200233

出　　处：《中西医结合心脑血管病杂志》2022年第22期4110-4114,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：上海市科委2019年度“科技创新行动计划”临床医学领域科技支撑项目(No.19401970600);上海市科委中医引导类项目(No.19401932500);上海市第六人民医院2022年度抗击新冠肺炎疫情应急专题项目(No.ynxg202218);上海市进一步加快中医药传承创新发展三年行动计划(2021年—2023年)项目[No.ZY(2021-2023)-0205-04];华东片区及市级中医专科专病联盟建设项目[No.ZY(2021-2023)-0302]。

摘　　要：目的探讨梓醇-川芎嗪方(CT方)对阿尔茨海默病(AD)模型小鼠的作用及对水通道蛋白4表达的影响。方法将β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PS1dE9)双转基因模型小鼠50只随机分为模型组、盐酸多奈哌齐片(安理申)组、梓醇-川芎嗪方低剂量组(CT-L组)、梓醇-川芎嗪方中剂量组(CT-M组)、梓醇-川芎嗪方高剂量组(CT-H组),每组10只。同月龄C57BL/6J小鼠10只为对照组。安理申组、CT-L组、CT-M组及CT-H组小鼠每天给予相应剂量的安理申及梓醇-川芎嗪方灌胃。对照组和模型组小鼠每天给予等体积的生理盐水灌胃,各组均为每天1次,连续灌胃8周,进行Morris水迷宫行为学检测,测定丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及总抗氧化能力(T-AOC)水平,测定脑内β-淀粉样蛋白(Aβ)水平,检测水通道蛋白-4(AQP4)表达水平。结果梓醇-川芎嗪方可以明显缩短APPswe/PS1dE9双转基因小鼠的逃避潜伏期、游泳距离、首次到达平台时间,增加穿越平台次数,降低脑内可溶性及不可溶性Aβ_(1-40)、Aβ_(1-42)水平,升高海马体和血清SOD、CAT和T-AOC水平,降低MDA水平,上调室周脑组织AQP4蛋白表达水平(P<0.05)。结论梓醇-川芎嗪方可以有效提高AD模型小鼠的认知和记忆能力,作用优于安理申。其作用机制可能与降低AD模型小鼠脑组织中Aβ沉积、调节氧化应激、上调AD模型小鼠室周脑组织AQP4蛋白表达水平有关。Objective To investigate the effects of Catalpol-tetramethylpyrazine(CT)Prescription on Alzheimer′s disease(AD)model mice and the expression of aquaporin-4.Methods Fifty APPswe/PS1dE9 double transgenic mice were randomly divided into model group,Aricept group,CT low-dose group(CT-L group),CT medium-dose group(CT-M group),and CT high-dose group(CT-H group),with 10 mice in each group.Ten C57BL/6J mice of the same month were chosen as the control group.Mice in Aricept group,CT-L group,CT-M group,and CT-H group were administrated corresponding doses of Aricept and CT prescription every day.Mice in the control group and model group were given the same volume of normal saline by gavage every day,once a day in each group for 8 consecutive weeks.The Morris water maze behavior were tested.The levels of malonic dialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(T-AOC)were measured,and the levels ofβ-amyioid protein(Aβ)and aquaporin protein-4(AQP4)were measured.Results CT prescription could significantly shorten the escape latency(EL),swimming distance(SD),time of first arrival at the platform(TFAP),increase number of crossing platforms(NCP),and reduce level of soluble and insoluble Aβ_(1-40) and Aβ_(1-42) in the brain of APPswe/PS1dE9 double transgenic mice,increase the level of SOD,CAT,and T-AOC in hippocampus and serum,decrease the level of MDA,and up-regulate the expression of AQP4 protein in periventricular brain tissue(P<0.05).Conclusion CT prescription can effectively improve the cognitive and memory abilities of AD model mice,and its effects are superior to those of Aricept.Its underlying mechanism may be related with reducing deposition of Aβin brain tissue of AD model mice,regulating oxidative stress and up-regulating expression of AQP4 protein in periventricular brain tissue of AD model mice.

关 键 词：阿尔茨海默病 梓醇-川芎嗪方 β-淀粉样蛋白沉积 氧化应激 水通道蛋白-4 实验研究 

分 类 号：R285.5[医药卫生—中药学]