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.
作者
单艳玲
张胜楠
崔丽杰
吴宿慧
李根林
李寒冰
SHAN Yanling;ZHANG Shengnan;CUILijie;WU Suhui;LI Genlin;LI Hanbing(Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
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)。
