基于APP/BACE1/Aβ信号通路的人参皂苷Rg1对AD树鼩模型的神经保护作用  

Neuroprotective effect of ginsenoside Rg1 based on the APP/BACE1/Aβsignaling pathway on Alzheimer’s tree shrew model

作　　者：吴超[1] 袁鑫[2] 郑红 tree shrew model WU Chao;YUAN Xin;ZHENG Hong(Parmacy Department,The First Affiliated Hospital of University of Science and Technology of China(Hefei Ion Medical Center),Anhui Hefei 230088,China;Pharmacy Department,The First Affiliated Hospital,Kunming Medical University,Yunnan Kunming 650500,China;Department of Laboratory Animal Science,Kunming Medical University,Yunan Kunming 650500,China)

机构地区：[1]中国科学技术大学附属第一医院离子医学中心(合肥离子医学中心)药剂科,安徽合肥230088 [2]昆明医科大学第一附属医院药剂科,云南昆明650500 [3]昆明医科大学实验动物学部,云南昆明650500

出　　处：《中国医院药学杂志》2024年第1期18-22,34,共6页Chinese Journal of Hospital Pharmacy

基　　金：云南省基础应用研究计划项目(编号:2017FE468-016)。

摘　　要：目的:观察人参皂苷Rg1对阿尔茨海默病(Alzheimer’s disease,AD)树鼩模型的行为学、病理形态学影响,研究其对APP-Aβ通路和bax、bcl-2蛋白水平的影响。方法:选取造模后树鼩60只,随机数字表法平均分为6组。假手术组:术后生理盐水灌胃8周;模型组:造模后生理盐水灌胃8周;阳性对照组:造模后连续多奈哌齐3 mg·kg^(–1)·d^(–1)灌胃8周;低中高剂量组:造模后分别连续人参皂苷Rg17.5,15,30 mg·kg^(–1)·d^(–1)灌胃8周。观察各组树鼩行为学变化、大脑细胞形态学变化,免疫组化分析Aβ_(1~42)蛋白变化,Western blot分析APP、BACE1、bax和bcl-2蛋白水平变化。结果:(1)水迷宫(morris water maze,MWM)行为学提示,经中高剂量人参皂苷Rg1治疗后模型树鼩认知功能明显改善。(2)HE染色提示模型树鼩海马细胞排列紊乱,离散程度极高,经过人参皂苷Rg1处理后显著缓解。(3)免疫组化提示模型树鼩Aβ_(1~42)蛋白表达显著提升,而中高剂量组树鼩Aβ_(1~42)蛋白表达显著降低;(4)Western blot结果提示各组树鼩脑内APP表达不受影响,而中高剂量组树鼩BACE1、bax蛋白表达水平显著降低,bcl-2蛋白表达明显上升。结论:人参皂苷Rg1能改善AD模型树鼩认知功能障碍,降低Aβ_(1~42)的表达,改善细胞凋亡,其机制可能与调节BACE1、bcl-2和bax等蛋白表达相关。OBJECTIVE To investigate the impact of ginsenoside Rg1 on behavioral and pathological aspects in an AD tree shrew model and its influence on the APP-Aβpathway,bax,and bcl-2 protein levels.METHODS Sixty tree shrews were ran⁃domly assigned to six groups after modeling.Sham surgery group received 8-week gastric lavage with saline,model group received the same treatment for 8 weeks after modeling,positive control group received gastric lavage with donepezil(3 mg·kg^(–1)·d^(–1))for continuous 8 weeks after modeling,and low,medium,and high-dose groups received 8-week ginsenoside Rg1(7.5,15,30 mg·kg^(–1)·d^(–1))after modeling.Behavioral observations,cellular morphology changes,Aβ_(1~42) protein(immunohistochemis⁃try),and protein levels of APP,BACE1,bax,and bcl-2(Western blot)were assessed.RESULTS(1)Morris water maze(MWM)showed improved cognitive function in model tree shrews treated with medium to high dose of ginsenoside Rg1.(2)Hematoxylin and eosin staining revealed significant hippocampal cell arrangement improvement after ginsenoside Rg1 treatment.(3)Immunohistochemistry indicated increased Aβ_(1~42) expression in model tree shrews,while significantly reduced in medium to high-dose ginsenoside Rg1 groups.(4)Western blot showed no impact on APP expression,while significant decrease in BACE1 and bax expression,and increase in bcl-2 expression in medium to high-dose ginsenoside Rg1 group.CONCLUSION Ginsen⁃oside Rg1 improves cognitive function,reduces Aβ_(1~42) expression,and mitigates apoptosis in the AD tree shrew model,poten⁃tially through regulating BACE1,bcl-2,and bax expression.

关 键 词：阿尔茨海默病 人参皂苷RG1 树鼩 APP BACE1 AΒ 

分 类 号：R965[医药卫生—药理学]