针刺研究2026，Vol.51Issue(9)：1178-1188,11.DOI:10.13702/j.1000-0607.20251094
电针调控HIF-1α/PFKFB3信号通路改善阿尔茨海默病小鼠糖酵解的机制研究
Electroacupuncture improves glycolysis in Alzheimer's disease model mice via regulating HIF-1α/PFKFB3 signaling pathway
摘要
Abstract
Objective To observe the effect of electroacupuncture(EA)on the cognitive ability,hypoxia-inducible factor-1 alpha(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)signaling pathway and glycolytic function in the hippocampus of Alzheimer's disease(AD)model mice,so as to elucidate its potential mechanism underlying improvement of cognitive function.Methods Male APP/PS1 transgenic mice were used as the AD model and randomly divided into model,EA and EA plus dimethyloxaloylglycine(DMOG,antagonist of α-ketoglutarate cofactor and inhibitor of HIF prolylhydroxylase)groups(n=6 each).Age-matched C57BL/6J mice served as the control group(n=6).EA stimulation(2 Hz,1 mA)was applied to bilateral"Shenshu"(BL23)and"Zusanli"(ST36),acupuncture was applied to"Baihui"(GV20)for 20 min,once every other day for 4 weeks.The mice in the EA+DMOG group was received intraperitoneal injection of DMOG(50 mg/kg)solution on the basis of EA starting from the 4th week.The mouse's cognitive function was evaluated by using Morris water maze and novel object recognition tests.Hematoxylin-eosin(H.E.)staining and immunohistochemistry were used to observe hippocampal neuronal morphology and β-amyloid(Aβ)1-42 deposition.The contents of pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)in the hippocampal tissue were assayed using ELISA,and the activity of hippocampal hexokinase(HK)and content of lactic acid were detected using biochemical methods.Western blot was employed to detect the expression levels of hippocampal HIF-1α and PFKFB3 protein,and real-time quantitative PCR was employed to detect the expression levels of hippocampal HIF-1α,PFKFB3,HK,PKM2,and LDHA mRNAs.The immunofluorescence histochemistry technique was used to measure the fluorescence intensity of hippocampal LDHA.Results Compared with the control group,the model group showed significantly longer escape latency,fewer platform crossings and lower novel object recognition index(P<0.01).After EA intervention,the escape latency was evidently shorter,the platform crossings and the novel object recognition index were apparently increased in the EA group(P<0.01),suggesting an improvement of the recognition ability and learning-memory ability.Following administration of DMOG,the effects of EA in shortening the escape latency,and increasing the number of platform crossings and novel object recognition index were eliminated(P<0.01,P<0.05,compared with the EA group).In contrast to the control group,the model group had a considerable increase in the optical density of Aβ1-42,contents of PKM2,LDHA,lactate,and HK activity,expression levels of HIF-1α and PFKFB3 proteins and mRNAs,and HK,PKM2,LDHA mRNAs,and LDHA fluorescence density(P<0.01).Compared with the model group,the increased levels of Aβ1-42 optical density,contents of PKM2,LDHA,lactate and HK activity,expression levels of HIF-1α and PFKFB3 proteins and mRNAs,and HK,PKM2,LDHA mRNAs,and LDHA fluorescence density were all reversed in the EA group(P<0.01).In comparison with the EA group,the decreased levels of Aβ1-42 optical density,contents of PKM2,LDHA,lactate,and HK activity,expression levels of HIF-1α and PFKFB3 proteins and mRNAs,and HK,PKM2,LDHA mRNAs,and LDHA fluorescence intensity were reversed by EA+DMOG(P<0.01,P<0.05).HE staining showed swollen or disintegrated neuronal cell bodies in the hippocampal CA1 region,deepened nuclear staining and expanded intercellular space in the model group.In comparison with the model group,the EA group(not the EA+DMOG group)displayed relatively intact nuclei of neurons,mitigated swelling of cell body and reduction in the infiltration of inflammatory cells and uniform distribution of cells in the CA1 region.Conclusion EA can significantly improve the cognitive function in AD model mice,which may be related to its function in inhibiting the hippocampal HIF-1α/PFKFB3 signaling pathway to reduce glycolytic enzyme activity and abnormal lactate accumulation.关键词
阿尔茨海默病/电针/糖酵解/认知功能/低氧诱导因子1α/磷酸果糖激酶双功能酶3Key words
Alzheimer's disease/Electroacupuncture/Glycolysis/Cognitive ability/Hypoxia-inducible factor-1α/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3引用本文复制引用
於赵勰,汪瑶,李亚楠,吕春凤,李军令,张洵,冯智鹏,沈峰,王彦春..电针调控HIF-1α/PFKFB3信号通路改善阿尔茨海默病小鼠糖酵解的机制研究[J].针刺研究,2026,51(9):1178-1188,11.基金项目
国家自然科学基金项目(No.82405575) （No.82405575）
湖北省自然科学基金项目(No.2023AFD113) （No.2023AFD113）
湖北省中医药管理局科研项目(No.ZY2023F13) （No.ZY2023F13）
湖北省中医药重点学科(针灸学)创新项目(No.XK202405) （针灸学）
湖北中医药大学2025年度博士研究生创新能力项目(No.2025BSCX05) （No.2025BSCX05）
湖北省时珍人才工程项目(No.鄂卫函[2024]256号) （No.鄂卫函[2024]256号）
