环球中医药2026，Vol.19Issue(6)：1189-1199,11.DOI:10.3969/j.issn.1674-1749.2026.06.007
电针抑制PI3K/Akt/mTOR通路促进分子伴侣介导的自噬保护帕金森病研究
Electroacupuncture protects against Parkinson's disease by promoting chaperone-mediated autophagy via inhibition of the PI3K/Akt/mTOR signaling pathway
摘要
Abstract
Objective To investigate the regulatory mechanism of electroacupuncture(EA)at"Baihui"(GV20)and"Shenshu"(BL23)on chaperone-mediated autophagy(CMA)in a mouse model of Parkinson's disease(PD).Methods Twenty-seven C57BL/6 mice were randomly assigned to three groups:the control group,the model group,and the EA group(n=9 per group).PD models were established in the model group and the EA group by intraperitoneal injection of MPTP.Mice in the EA group received EA treatment at GV20 and BL23(continuous wave,2 Hz,2 mA,15 min/day)for 14 con-secutive days.Motor performance was evaluated using the rotarod test,suspension test,pole test,and gait analysis.Tyrosine hydroxylase(TH)immunofluorescence and double staining for neuronal nuclei(NeuN)with lysosome-associated membrane protein 2A(LAMP2A)or heat shock cognate protein 70(HSC70)were used to assess dopaminergic neuronal survival and CMA activity in the substantia nigra.The method of western blotting was performed to determine the protein levels of TH,α-synuclein(α-syn),phosphatidylinositol 3-kinases(PI3K),protein kinase B(Akt),p-Akt,mammalian target of rapamycin(mTOR),p-mTOR,LAMP2A,HSC70,glial fibrillary acidic protein(GFAP),and transcription factor EB(TFEB)in the substantia nigra,while RT-qPCR was used to detect mRNA expression of PI3K,Akt,and mTOR.Results Compared with the control group,the model group showed a significantly decreased rotarod latency(P＜0.01),decreased suspension test scores(P＜0.01),prolonged pole-climbing time(P＜0.01),and decreased stride length and increased step frequency(P＜0.01).TH fluorescence intensity in the substantia nigra was markedly reduced(P＜0.01),and the colocalization of NeuN with LAMP2A or HSC70 was decreased(P＜0.05,P＜0.01).The expression of PI3K,p-Akt/Akt,p-mTOR/mTOR,α-syn,and GFAP were increased(P＜0.05,P＜0.01,P＜0.05,P＜0.05,P＜0.01),while TFEB expression were decreased(P＜0.01);mRNA levels of PI3K,Akt,and mTOR were elevated(P＜0.01).Compared with the model group,EA significantly prolonged rotarod latency(P＜0.01),increased suspension test scores(P＜0.05),shortened pole-climbing time(P＜0.01),and improved gait coordination(P＜0.05).EA increased TH-positive neuronal fluorescence intensity(P＜0.01),enhanced NeuN colocalization with LAMP2A and HSC70(P＜0.05,P＜0.01),reduced PI3K,p-Akt/Akt,p-mTOR/mTOR,α-syn and GFAP expression(P＜0.05,P＜0.01,P＜0.01,P＜0.05,P＜0.05)and up-regulated TFEB(P＜0.01).Moreover,EA decreased mRNA levels of PI3K,Akt,and mTOR(P＜0.01,P＜0.01,P＜0.05).Conclusion EA may exert neuroprotective effects against PD by modulating the PI3K/Akt/mTOR signaling pathway to activate neuron-specific CMA,thereby promoting α-syn clearance and alleviating neuroinflammation.关键词
电针/帕金森病/分子伴侣介导的自噬/磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号转导通路/α-突触核蛋白/转录因子EB/溶酶体相关膜蛋白2A/多巴胺能神经元Key words
electroacupuncture/Parkinson's disease/chaperone-mediated autophagy/PI3K/Akt/mTOR signaling pathway/α-synuclein/transcription factor EB/lysosome-associated membrane protein 2A/dopaminergic neurons分类
医药卫生引用本文复制引用
唐祎泽,樊慧杰,王旭,柴智,刘洋,肖楷楠,崔鸿鹏,徐磊,肖圣男,张天生,郝重耀,王海军..电针抑制PI3K/Akt/mTOR通路促进分子伴侣介导的自噬保护帕金森病研究[J].环球中医药,2026,19(6):1189-1199,11.基金项目
国家中医药管理局青年岐黄学者培养项目(国中医药人教函[2022]256号) （国中医药人教函[2022]256号）
山西省重点科技创新人才团队专项(202304051001019) （202304051001019）
山西省重点国别科技合作项目(202204041101002,202404041101011) （202204041101002,202404041101011）
山西省青年拔尖人才支持计划项目(晋组办字[2019]35号文) （晋组办字[2019]35号文）
山西省省筹资金资助回国留学人员科研项目(2021-142) （2021-142）
山西省卫健委中医药重点研究室建设专项(zyyyjs2024022) （zyyyjs2024022）
山西省卫健委中医药创新团队建设专项(yytd2024022) （yytd2024022）
山西中医药大学科技创新团队建设项目(2022TD1013) （2022TD1013）
