基于Aβ和Tau转基因线虫探讨20(S)-原人参二醇抗阿尔茨海默病的作用及机制  

Effects and mechanism of 20(S)-protopanaxadiot on alleviating the neurotoxicity of Alzheimer's disease in Aβ and Tau transgenic Caenorhabditis elegans

作　　者：单艳玲 张胜楠 崔丽杰 吴宿慧[1] 李根林[1] 李寒冰[1] SHAN Yanling;ZHANG Shengnan;CUILijie;WU Suhui;LI Genlin;LI Hanbing(Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,郑州450046

出　　处：《中华中医药杂志》2023年第10期4907-4912,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河南省科技攻关项目(No.192102310173);河南省中医药科学研究专项(No.20-21ZY1038)。

摘　　要：目的:探讨20(S)-原人参二醇(PPD)对β淀粉样蛋白(Aβ)和Tau两种转基因线虫的治疗作用及可能的机制。方法:采用CL4176线虫(Aβ)和BR5270线虫(Tau)模型,测定不同浓度PPD对两种线虫瘫痪、寿命、摆动次数、短期和长期联想记忆的影响,并采用RT-qPCR法检测线虫体内相关基因的表达。结果:PPD可以显著延缓CL4176线虫瘫痪、延长BR5270线虫寿命(P<0.01),提高BR5270线虫的摆动次数(P<0.01),提高BR5270线虫的摆动次数,但对CL4176线虫的摆动次数没有影响;PPD50、100μmol/L给药后,两种线虫的短期记忆、长期联想记忆学习指数在各个时间点均显著提高。PPD各给药组均能显著降低两种线虫体内AGE-1、AKT-1和GSK-3 mRNA表达并上调CED-9 mRNA表达。结论:PPD可以抑制Aβ和Tau蛋白的毒性,具有神经保护作用,其机制可能与调节PI3K/Akt信号通路有关。Objective:To investigate the therapeutic effect and possible mechanism of 20(S)-protopanaxadiol(PPD)on Aβ and Tau transgenic Caenorhabditis elegans(C.elegans).Methods:The CL4176 nematode(Aβ)and BR5270 C.elegans(Tau)models were used to determine the effects of PPD on paralysis,lifespan,number of swings,short-term and long-term associative memory and RT-qPCR was used to detect the expression of AD related genes in the C.elegans.Results:PPD could delay the paralysis of CL4176 C.elegans and prolong the lifespan of BR5270 C.elegans(P<0.01);increase the swing times of BR5270 C.elegans.PPD 50,100μmol/L group could increase the short-term and long-term associative memory learning index of the two transgenic C.elegans.PPD 25,50 and 100μmol/L groups decrease AGE-1,AKT-1,and GSK-3 mRNA expression,and upregulate CED-9 mRNA expression in the two transgenic C.elegans.Conclusion:PPD could inhibit the toxicity of Aβ and Tau proteins and has neuroprotective effects,and its mechanism may be related to the regulation of PI3K/Akt signaling pathway.

关 键 词：20(S)-原人参二醇 阿尔茨海默病 秀丽隐杆线虫 学习记忆 痴呆 Β淀粉样蛋白 TAU 

分 类 号：R285[医药卫生—中药学]