BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent i...BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent information regulator type 2 homolog-1(SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α(PGC-1α)axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy(T2DPN),potentially breaking this harmful cycle.AIM To validate the effectiveness of electroacupuncture(EA)in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1αaxis.METHODS The effects of EA were evaluated through assessments of metabolic changes,morphological observations,and functional examinations of the sciatic nerve,along with measurements of inflammation and oxidative stress.Proteins related to the SIRT1/PGC-1αaxis,involved in the regulation of mitochondrial biogenesis and antioxidative stress,were detected in the sciatic nerve using Western blotting to explain the underlying mechanism.A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis.RESULTS In addition to diabetes-related metabolic changes,T2DPN rats showed significant reductions in pain threshold after 9 weeks,suggesting abnormal peripheral nerve function.EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats.The SIRT1/PGC-1αaxis,which was downregulated in the model group,was upregulated by EA intervention.The endogenous antioxidant system related to the SIRT1/PGC-1αaxis,previously inhibited in diabetic rats,was reactivated.A similar trend was observed in inflammatory markers.When SIRT1 was inhibited in diabetic rats,these beneficial effects were abolished.CONCLUSION EA can alleviate the symptoms of T2DNP in experimental rats,and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1αaxis.展开更多
背景:骨骼肌线粒体生物合成及其运动调控机制是目前的研究焦点。腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶、钙调信号等通路于运动诱导的线粒体生物合成意义深远,关乎肌肉代谢优化、运动表...背景:骨骼肌线粒体生物合成及其运动调控机制是目前的研究焦点。腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶、钙调信号等通路于运动诱导的线粒体生物合成意义深远,关乎肌肉代谢优化、运动表现提升与代谢病预防。然而,各通路的相互作用、调控机制及其在运动对骨骼肌线粒体生物合成的综合效应尚不清楚。目的:探讨骨骼肌线粒体生物合成相关信号通路,精准解析运动在其中的诱导及调控细节,阐释运动激活信号通路促进线粒体生成与功能强化的原理,为改善肌肉代谢、提升运动效能、预防代谢疾病筑牢理论根基。方法:通过检索中国知网(CNKI)、万方、维普等中文数据库,以及PubMed、Web of Science等英文数据库,收集自建库至2024年8月发表的与骨骼肌线粒体生物合成及其调控机制相关的最新文献。结合多条信号通路的研究结果,系统梳理了运动对线粒体生物合成的调控机制,重点关注腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、蛋白激酶A、丝裂原活化蛋白激酶、钙调信号通路的相互作用和协同机制。结果与结论:①骨骼肌线粒体生物合成是一个复杂的生物学过程,涉及多条信号通路的协同调控,旨在根据能量需求和外界应激的变化,优化骨骼肌的代谢能力、抗疲劳性以及整体运动表现,其核心机制包括腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶等关键因子的相互作用和调节。②腺苷酸活化蛋白激酶通过感知细胞能量状态,激活过氧化物酶体增殖物激活受体γ共激活因子1α,促进线粒体生物合成。而过氧化物酶体增殖物激活受体γ共激活因子1α作为骨骼肌线粒体生物合成的主要调控因子,能够调节线粒体蛋白和DNA的合成,增强抗氧化应激反应,提升线粒体功能。③丝裂原活化蛋白激酶信号通路,特别是丝裂原活化蛋白激酶p38,在应激反应中通过激活过氧化物酶体增殖物激活受体γ共激活因子1α进一步促进线粒体生成。④此外,钙调信号通路和PKA信号通路亦在骨骼肌的代谢调节中扮演着重要角色。⑤运动能够通过激活上述多条信号通路,显著提高骨骼肌的线粒体生物合成能力,优化细胞的代谢效率,增强肌肉耐力,改善运动表现。⑥未来研究可聚焦于深入探讨腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶和钙调信号在不同运动强度和模式下的交互机制;加强对不同年龄、性别及健康状况群体的研究;验证研究成果的普适性与群体特异性;挖掘新兴调控因子如FNIP1、PERM1的精细机制及其在运动干预中的潜力;以及推动运动健康研究成果向临床应用转化等。展开更多
基金National Natural Science Foundation of China,No.82074532,No.82374577,No.82305375,No.82305376,and No.82405567The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent information regulator type 2 homolog-1(SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α(PGC-1α)axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy(T2DPN),potentially breaking this harmful cycle.AIM To validate the effectiveness of electroacupuncture(EA)in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1αaxis.METHODS The effects of EA were evaluated through assessments of metabolic changes,morphological observations,and functional examinations of the sciatic nerve,along with measurements of inflammation and oxidative stress.Proteins related to the SIRT1/PGC-1αaxis,involved in the regulation of mitochondrial biogenesis and antioxidative stress,were detected in the sciatic nerve using Western blotting to explain the underlying mechanism.A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis.RESULTS In addition to diabetes-related metabolic changes,T2DPN rats showed significant reductions in pain threshold after 9 weeks,suggesting abnormal peripheral nerve function.EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats.The SIRT1/PGC-1αaxis,which was downregulated in the model group,was upregulated by EA intervention.The endogenous antioxidant system related to the SIRT1/PGC-1αaxis,previously inhibited in diabetic rats,was reactivated.A similar trend was observed in inflammatory markers.When SIRT1 was inhibited in diabetic rats,these beneficial effects were abolished.CONCLUSION EA can alleviate the symptoms of T2DNP in experimental rats,and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1αaxis.
文摘背景:骨骼肌线粒体生物合成及其运动调控机制是目前的研究焦点。腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶、钙调信号等通路于运动诱导的线粒体生物合成意义深远,关乎肌肉代谢优化、运动表现提升与代谢病预防。然而,各通路的相互作用、调控机制及其在运动对骨骼肌线粒体生物合成的综合效应尚不清楚。目的:探讨骨骼肌线粒体生物合成相关信号通路,精准解析运动在其中的诱导及调控细节,阐释运动激活信号通路促进线粒体生成与功能强化的原理,为改善肌肉代谢、提升运动效能、预防代谢疾病筑牢理论根基。方法:通过检索中国知网(CNKI)、万方、维普等中文数据库,以及PubMed、Web of Science等英文数据库,收集自建库至2024年8月发表的与骨骼肌线粒体生物合成及其调控机制相关的最新文献。结合多条信号通路的研究结果,系统梳理了运动对线粒体生物合成的调控机制,重点关注腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、蛋白激酶A、丝裂原活化蛋白激酶、钙调信号通路的相互作用和协同机制。结果与结论:①骨骼肌线粒体生物合成是一个复杂的生物学过程,涉及多条信号通路的协同调控,旨在根据能量需求和外界应激的变化,优化骨骼肌的代谢能力、抗疲劳性以及整体运动表现,其核心机制包括腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶等关键因子的相互作用和调节。②腺苷酸活化蛋白激酶通过感知细胞能量状态,激活过氧化物酶体增殖物激活受体γ共激活因子1α,促进线粒体生物合成。而过氧化物酶体增殖物激活受体γ共激活因子1α作为骨骼肌线粒体生物合成的主要调控因子,能够调节线粒体蛋白和DNA的合成,增强抗氧化应激反应,提升线粒体功能。③丝裂原活化蛋白激酶信号通路,特别是丝裂原活化蛋白激酶p38,在应激反应中通过激活过氧化物酶体增殖物激活受体γ共激活因子1α进一步促进线粒体生成。④此外,钙调信号通路和PKA信号通路亦在骨骼肌的代谢调节中扮演着重要角色。⑤运动能够通过激活上述多条信号通路,显著提高骨骼肌的线粒体生物合成能力,优化细胞的代谢效率,增强肌肉耐力,改善运动表现。⑥未来研究可聚焦于深入探讨腺苷酸活化蛋白激酶、过氧化物酶体增殖物激活受体γ共激活因子1α、丝裂原活化蛋白激酶和钙调信号在不同运动强度和模式下的交互机制;加强对不同年龄、性别及健康状况群体的研究;验证研究成果的普适性与群体特异性;挖掘新兴调控因子如FNIP1、PERM1的精细机制及其在运动干预中的潜力;以及推动运动健康研究成果向临床应用转化等。
