智脑胶囊对阿尔茨海默病小鼠认知功能的影响及机制初探  

Effect and Mechanism of Zhinao(智脑)Capsules on Cognitive Function of Mice with Alzheimer's Disease

作　　者：姜辉[1] 马艳珍 汪永忠[1] 杨文明[1] JIANG Hui;MA Yanzhen;WANG Yongzhong;YANG Wenming(The First Hospital Affiliated to Anhui University of Chinese Medicine,Hefei 230031)

机构地区：[1]安徽中医药大学第一附属医院,合肥230031

出　　处：《中药药理与临床》2023年第2期13-18,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：安徽省科技重大专项项目(编号:201903a07020016)。

摘　　要：目的:阐明智脑胶囊对阿尔茨海默病(Alzheimer’s Disease, AD)小鼠认知功能的影响及可能机制。方法:采用D-半乳糖联合亚硝酸钠复制AD小鼠模型,分别灌胃给予0.98、1.95、3.90 g/kg智脑胶囊和阳性药石杉碱甲片0.21 mg/kg,利用水迷宫、八臂迷宫、穿梭箱等试验,观察AD小鼠认知功能;HE染色法观察海马组织病理学改变,免疫组化法检测海马组织中淀粉样前体蛋白(Recombinant Amyloid Precursor Protein, APP)表达情况,实时荧光定量PCR及Western Blot法检测海马组织中磷脂酰肌醇3激酶/蛋白激酶B/糖原合成酶激酶-3β(Pi3k/Akt/Gsk3b)mRNA及蛋白表达。结果:与正常对照组相比,模型对照组小鼠寻找平台潜伏期明显延长,工作记忆和参考记忆错误次数显著增多,主动逃避有害刺激次数明显降低,海马DG区神经元细胞间隙明显增宽,排列紊乱,Gsk3b mRNA及APP、GSK-3β蛋白表达显著上调,p-PI3K/PI3K、p-AKT/AKT值显著降低(P<0.05或P<0.01);与模型对照组比较,智脑胶囊1.95、3.9 g/kg组和石杉碱甲片0.21 mg/kg组不仅可明显缩短小鼠寻找平台潜伏期,降低工作记忆和参考记忆错误次数,提高主动逃避有害刺激次数,改善病理组织学损伤程度,还能明显下调海马组织中Gsk3b mRNA、APP、GSK-3β蛋白表达,明显升高p-PI3K/PI3K和p-AKT/AKT值(P<0.05或P<0.01)。结论:智脑胶囊改善AD小鼠认知功能,可能与调控PI3K/AKT/GSK-3β信号通路有关。Objective:To elucidate the effect and underlying mechanism of Zhinao(智脑)Capsules on the cognitive function of mice with Alzheimer's disease(AD).Methods:The AD model was induced by D-galactose combined with sodium nitrite in mice,and the model mice were treated with Zhinao Capsules(0.98,1.95,and 3.90 g/kg)and positive drug huperzine A tablets(0.21 mg/kg)by gavage.The cognitive function of AD mice was observed by the Morris water maze test,the radial arm maze test,and the shuttle box test.Histopathological changes in the hippocampus were observed by Hematoxylin-Eosin(HE)staining.Immunohistochemistry was performed to detect the recombinant amyloid precursor protein(APP)expression in hippocampal tissues.RT-qPCR and Western blot were used to detect the mRNA and protein expression levels of phosphatidylinositol-3-kinase Pi3h)/protein kinase B(Akt)/glycogen synthase kinase-3β(Gsk3β)in hippocampal tssues.Results:Compared with the normal group,the model mice showed longer latency of platform seeking,increased working and reference memory errors,reduced active avoidance of noxious stimuli,widened intercellular space of neurons in the DG region of the hippocampus,disordered arrangement of neurons,up-regulated Gsk3βmRNA expression and APP and GSK-3βprotein expression,and decreased protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05 or P<0.01).Compared with the model group,the Zhinao Capsules groups(1.95 and 3.9 g/kg)and huperzine A tablets group(0.21 mg/kg)showed shortened latency period of platform seeking,reduced working and reference memory errors,increased active avoidance of noxious stimuli,improved pathological histological damage,inhibited Gsk3βmRNA expression and APP and GSK-3βprotein expression,and elevated p-PI3K/PI3K and p-Akt/Akt protein expression in hippocampal tissues(P<0.05 or P<0.01).Conclusion:Zhinao Capsules play a role in improving cognitive function in AD mice,and the mechanism is attributed to the regulation of the PI3K/Akt/GSK-3βsignaling pathway.

关 键 词：智脑胶囊 阿尔茨海默病 认知功能 磷脂酰肌醇3激酶/蛋白激酶B/糖原合成酶激酶-3β信号通路 

分 类 号：R285.5[医药卫生—中药学]