银杏叶提取物联合多奈哌齐对阿尔茨海默病模型大鼠的协同作用及其机制  

Synergistic Effect of Extract of Ginkgo Biloba Leaves Combined with Donepezil on Alzheimer′s Disease Model Rats and Its Mechanism

作　　者：薛艳云 李媛媛 王亚敏 王树锋 XUE Yanyun;LI Yuanyuan;WANG Yamin;WANG Shufeng(Shalingzi Hospital,Zhangjiakou,Hebei,China 075000;The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei,China 075000)

机构地区：[1]河北省张家口市沙岭子医院,河北张家口075000 [2]河北北方学院附属第一医院,河北张家口075000

出　　处：《中国药业》2024年第10期59-65,共7页China Pharmaceuticals

基　　金：河北省张家口市科技计划项目[2221145D]。

摘　　要：目的探讨银杏叶提取物(EGb 761)联合多奈哌齐对阿尔茨海默病(AD)模型大鼠的协同作用及其机制。方法取雄性SD大鼠72只,随机分为正常组(等体积生理盐水)、假手术组(等体积生理盐水)、模型组(等体积生理盐水)、多奈哌齐组(25 mg/kg)、EGb 761组(50 mg/kg)和联合组(多奈哌齐25 mg/kg+EGb 76150 mg/kg),各12只。腹膜内注射水合氯醛300 mg/kg麻醉,将聚集的Aβ25-35(10μL)以1μL/min的速率注入大鼠双侧海马,以复制AD大鼠模型。建模成功后,各组大鼠均灌胃相应药物或生理盐水,每天1次,共2个疗程(每个疗程10 d,间隔3 d)。采用Morris水迷宫实验评估大鼠的认知和记忆能力;采用TUNEL染色法,观察大鼠海马神经细胞凋亡情况,并计算凋亡指数;采用酶联免疫吸附法检测大鼠血清乙酰胆碱酯酶(AChE)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;采用Western blot法检测大鼠海马组织中核因子(NF)-κB通路相关蛋白p-IKKα,p-IκBα,p-NF-κB表达水平。结果与模型组比较,各给药组大鼠Morris水迷宫实验第6天逃避潜伏期均大幅缩短,第7天各给药组大鼠在象限Ⅰ中穿越平台的次数及耗时百分比均显著增加;各给药组大鼠海马神经细胞阳性数量均显著减少,凋亡指数均显著降低(P<0.05);各给药组大鼠AChE和MDA水平均显著降低,SOD水平显著升高(P<0.05);各给药组大鼠NF-κB通路相关蛋白p-IKKα,p-IκBα,p-NF-κB的表达水平均显著升高(P<0.05);且联合组上述指标变化均更显著(P<0.05)。结论EGb 761联合多奈哌齐可协同改善AD模型大鼠的记忆能力,其机制可能与减少海马神经细胞NF-κB通路激活后的细胞凋亡有关。Objective To investigate the synergistic effect of extract of Ginkgo biloba leaves(EGb 761)combined with donepezil on the Alzheimer′s disease(AD)model rats and its mechanism.Methods A total of 72 male SD rats were selected and randomly divided into the normal group(equal volume of normal saline),the sham operation group(equal volume of normal saline),the model group(equal volume of normal saline),the donepezil group(25 mg/kg),the EGb 761 group(50 mg/kg),and the combination group(25 mg/kg donepezil+50 mg/kg EGb 761),with 12 rats in each group.After intraperitoneal injection of 300 mg/kg chloral hydrate for anesthesia,the rats′bilateral hippocampi were injected into the aggregated Aβ25-35(10μL)at a rate of 1μL/min to replicate the AD rat models.After successful modeling,the rats in each group were given corresponding drug or normal saline by gavage once a day for two treatment courses(10 d for each course,with an interval of 3 d).The Morris water maze test was used to assess the cognitive and memory abilities of rats.The TUNEL staining method was used to observe the apoptosis of hippocampal neurons in rats,and the apoptotic index was calculated.The enzyme-linked immunosorbent assay(ELISA)was used to detect the serum acetylcholinesterase(AChE),malondialdehyde(MDA)and superoxide dismutase(SOD)levels in rats.The Western blot was used to detect the expression levels of nuclear factor(NF)-κB pathway-related proteins including p-IKKα,p-IκBαand p-NF-κB in hippocampal tissue of rats.Results Compared with those in the model group,the escape latency in each drug group significantly shortened on the 6th day of Morris water maze test,the frequency of crossing the platform and time-consuming percentage in quadrantⅠsignificantly increased on the 7th day;the positive cell count and the apoptotic index of hippocampal neurons in each drug group significantly decreased(P<0.05);the AChE and MDA levels in each drug group significantly decreased,while the SOD level significantly increased(P<0.05);the expression levels of

关 键 词：银杏叶提取物 多奈哌齐 EGb 761 阿尔茨海默病 核因子-κB通路 认知功能 细胞凋亡 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]