中药调控AMPK信号通路治疗糖尿病肾病的研究进展
Research Progress on the Treatment of Diabetic Nephropathy by Traditional Chinese Medicine through Regulating the AMPK Signaling Pathway
DOI: 10.12677/tcm.2025.146361, PDF,   
作者: 赵 丹：黑龙江中医药大学研究生院，黑龙江 哈尔滨；马国庆*：黑龙江中医药大学附属第二医院内分泌科，黑龙江 哈尔滨
关键词: 中药；糖尿病肾病；AMPK信号通路；Traditional Chinese Medicine； Diabetic Nephropathy； AMPK Signaling Pathway
摘要: 糖尿病肾病(Diabetic Nephropathy DN)是糖尿病最常见的并发症之一，也是终末期肾病的主要原因。有大量研究表明，DN与AMP活化蛋白激酶(AMPK)信号通路之间有密切的关系，AMPK信号通路通过与细胞自噬、氧化应激和炎症反应等相互作用影响DN的进展。中医药在DN的临床治疗中起到重要作用，且中医药基于该机制防治DN的研究已取得较大进展。因此笔者从AMPK信号通路出发，阐述其干预DN的关键机制和相关研究进展，整理了基于该信号通路的中药单体活性成分或提取物、中药复方治疗DN的方法，以期为中医药治疗DN提供更多帮助。
Abstract: Diabetic Nephropathy, a common complication of diabetes, is a major cause of end-stage renal disease. Ample research indicates a close link between DN and the AMP-activated protein kinase signaling pathway, which impacts DN progression through regulating autophagy, oxidative stress, and inflammation. Traditional Chinese medicine is crucial in DN treatment, with significant progress in relevant prevention and treatment research. This paper reviews the key mechanisms of the AMPK pathway in DN intervention, and summarizes the application of traditional Chinese medicine monomers, extracts, and compound formulas for DN treatment, aiming to inform traditional Chinese medicine treatment of DN.
文章引用：赵丹, 马国庆. 中药调控AMPK信号通路治疗糖尿病肾病的研究进展[J]. 中医学, 2025, 14(6): 2440-2449. https://doi.org/10.12677/tcm.2025.146361

参考文献

[1] Magliano, D.J. and Boyko, E.J. (2021) IDF Diabetes Atlas. International Diabetes Federation.
[2] Entezari, M., Hashemi, D., Taheriazam, A., Zabolian, A., Mohammadi, S., Fakhri, F., et al. (2022) AMPK Signaling in Diabetes Mellitus, Insulin Resistance and Diabetic Complications: A Pre-Clinical and Clinical Investigation. Biomedicine & Pharmacotherapy, 146, Article 112563. [Google Scholar] [CrossRef] [PubMed]
[3] Ross, F.A., MacKintosh, C. and Hardie, D.G. (2016) AMP‐Activated Protein Kinase: A Cellular Energy Sensor That Comes in 12 Flavours. The FEBS Journal, 283, 2987-3001. [Google Scholar] [CrossRef] [PubMed]
[4] 孙宇石, 李柏均, 程帆. AMP活化蛋白激酶抑制肾纤维化的作用机制研究进展[J]. 山东医药, 2024, 64(14): 87-90.
[5] Ke, R., Xu, Q., Li, C., Luo, L. and Huang, D. (2017) Mechanisms of AMPK in the Maintenance of ATP Balance during Energy Metabolism. Cell Biology International, 42, 384-392. [Google Scholar] [CrossRef] [PubMed]
[6] Malik, N., Ferreira, B.I., Hollstein, P.E., Curtis, S.D., Trefts, E., Weiser Novak, S., et al. (2023) Induction of Lysosomal and Mitochondrial Biogenesis by AMPK Phosphorylation of Fnip1. Science, 380, eabj5559. [Google Scholar] [CrossRef] [PubMed]
[7] Stanigut, A.M., Tuta, L., Pana, C., Alexandrescu, L., Suceveanu, A., Blebea, N., et al. (2025) Autophagy and Mitophagy in Diabetic Kidney Disease—A Literature Review. International Journal of Molecular Sciences, 26, Article 806. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, S., Li, H., Yuan, M., Fan, H. and Cai, Z. (2022) Role of AMPK in Autophagy. Frontiers in Physiology, 13, Article 1015500. [Google Scholar] [CrossRef] [PubMed]
[9] Rabinowitz, J.D. and White, E. (2010) Autophagy and Metabolism. Science, 330, 1344-1348. [Google Scholar] [CrossRef] [PubMed]
[10] Velagapudi, C., Bhandari, B.S., Abboud-Werner, S., Simone, S., Abboud, H.E. and Habib, S.L. (2011) The Tuberin/mTOR Pathway Promotes Apoptosis of Tubular Epithelial Cells in Diabetes. Journal of the American Society of Nephrology, 22, 262-273. [Google Scholar] [CrossRef] [PubMed]
[11] Yu, J., Liu, Y., Li, H. and Zhang, P. (2023) Pathophysiology of Diabetic Kidney Disease and Autophagy: A Review. Medicine, 102, e33965. [Google Scholar] [CrossRef] [PubMed]
[12] Ge, Y., Zhou, M., Chen, C., Wu, X. and Wang, X. (2022) Role of AMPK Mediated Pathways in Autophagy and Aging. Biochimie, 195, 100-113. [Google Scholar] [CrossRef] [PubMed]
[13] Song, F., Song, M., Ma, W., Gao, Z., Ti, Y., Zhang, X., et al. (2021) Overexpressing STAMP2 Attenuates Diabetic Renal Injuries via Upregulating Autophagy in Diabetic Rats. Biochemical and Biophysical Research Communications, 579, 47-53. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, N. and Zhang, C. (2024) Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease. Antioxidants, 13, Article 455. [Google Scholar] [CrossRef] [PubMed]
[15] Lu, Q., Zhou, Y., Hao, M., Li, C., Wang, J., Shu, F., et al. (2018) The mTOR Promotes Oxidative Stress-Induced Apoptosis of Mesangial Cells in Diabetic Nephropathy. Molecular and Cellular Endocrinology, 473, 31-43. [Google Scholar] [CrossRef] [PubMed]
[16] Hashemi, M., Zandieh, M.A., Ziaolhagh, S., Mojtabavi, S., Sadi, F.H., Koohpar, Z.K., et al. (2023) Nrf2 Signaling in Diabetic Nephropathy, Cardiomyopathy and Neuropathy: Therapeutic Targeting, Challenges and Future Prospective. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1869, Article 166714. [Google Scholar] [CrossRef] [PubMed]
[17] Tian, H., Zheng, X. and Wang, H. (2023) Isorhapontigenin Ameliorates High Glucose-Induced Podocyte and Vascular Endothelial Cell Injuries via Mitigating Oxidative Stress and Autophagy through the AMPK/Nrf2 Pathway. International Urology and Nephrology, 55, 423-436. [Google Scholar] [CrossRef] [PubMed]
[18] Wu, S., Wu, Y., Wu, T. and Wei, Y. (2014) Role of AMPK-Mediated Adaptive Responses in Human Cells with Mitochondrial Dysfunction to Oxidative Stress. Biochimica et Biophysica Acta (BBA)-General Subjects, 1840, 1331-1344. [Google Scholar] [CrossRef] [PubMed]
[19] 姚烽, 汲广岩, 张力. 腺苷酸活化蛋白激酶: 炎症调控新靶点[J]. 生理学报, 2012, 64(3): 341-345.
[20] 张笑栩, 何毓玺, 王洁, 等. 糖肾清2号提取物调控AMPK信号通路对高糖环境下肾小球系膜细胞炎症因子表达的影响[J]. 中华中医药学刊, 2019, 37(4): 929-933.
[21] 陆世龙, 王龙龙, 黄国东. 中医药治疗早期糖尿病肾病的研究进展[J]. 辽宁中医杂志, 2016, 43(5): 1101-1103.
[22] 张晓东, 赵文卓, 韩美妮, 等. AMPK通路经细胞自噬调控慢性肾脏病及其中医药防治的研究进展[J]. 中药药理与临床: 1-19.
[23] 杨虎虎, 何泽, 南征. 从“瘀毒”论治消渴肾病机制探析[J]. 中医药学报, 2024, 52(2): 48-52.
[24] 夏其乐, 王涛, 陆胜民, 等. 苦杏仁苷的分析、提取纯化及药理作用研究进展[J]. 食品科学, 2013, 34(21): 403-407.
[25] 闫萌萌, 徐林丽, 刘岩岩, 等. 苦杏仁苷对糖尿病肾病大鼠肾小管上皮细胞损伤的影响[J]. 中国临床药理学杂志, 2024, 40(7): 1019-1023.
[26] 王文君, 杨泽敏, 刘安, 等. 知母化学成分、药理作用研究进展及其质量标志物预测分析[J]. 中国中药杂志, 2025, 50(4): 934-945.
[27] 张少泉, 倪向荣, 李鑫辉. 知母皂苷元通过AMPK-mTOR-ULK1途径抑制肾小球系膜基质合成和激活自噬治疗糖尿病肾病的研究[J]. 现代中西医结合杂志, 2021, 30(11): 1180-1186.
[28] 孙广平, 袁丽, 方晓琳, 等. 紫苏叶多糖改善2型糖尿病大鼠肝损伤的作用及机制研究[J]. 中药材, 2020, 43(11): 2798-2801.
[29] 薛剑, 乔晨. 紫苏叶提取物通过AMPK/mTOR自噬信号通路改善糖尿病肾病大鼠肾脏损伤研究[J]. 中医药学报, 2023, 51(9): 18-22.
[30] 昝珂, 钱正明, 李文佳, 等. 冬虫夏草繁育品质量控制和药理活性研究进展[J]. 中国药事, 2020, 34(4): 464-470.
[31] 李冰心, 许军英, 张雅茹, 等. 冬虫夏草通过调控AMPK/mTOR通路保护高糖诱导的足细胞损伤[J]. 天津医药, 2025, 53(3): 225-229.
[32] 陈红, 公欣华, 陈丽君, 等. 二氢杨梅素激活AMPK通路预防糖尿病肾病的作用研究[J]. 现代生物医学进展, 2017, 17(34): 6613-6619+6612.
[33] 刘旭峰, 冯佳, 王述进, 等. 黄芪多糖对糖尿病肾病大鼠氧化应激和自噬的影响及机制[J]. 山西医科大学学报, 2023, 54(3): 343-351.
[34] 姚艺, 李艳丽, 丁洪成, 等. 芒柄花苷经AMPK/SIRT1/FoxO1通路对2型糖尿病肾病大鼠肾损伤的改善作用[J]. 河北医学, 2022, 28(11): 1785-1790.
[35] 张婷. 甘草酸通过AMPK/SIRT1/PGC-1α信号通路对糖尿病肾病保护作用的研究[D]: [硕士学位论文]. 银川: 宁夏医科大学, 2018.
[36] 杨琳, 王蓉蓉, 郭小雨, 等. 小檗碱激活SIRT1/AMPK信号通路改善高糖诱导的系膜细胞异常增殖和自噬功能[J]. 安徽医科大学学报, 2023, 58(6): 896-901.
[37] 张正菊, 孟凤仙, 白华, 等. 虎杖苷对糖尿病肾病小鼠AMPKα1/TLR4信号通路的影响[J]. 中国中西医结合杂志, 2019, 39(11): 1378-1384.
[38] 张正菊, 张承承, 白华, 等. 大黄素对糖尿病肾病小鼠AMPKα1/TLR4/p65信号通路的影响[J]. 世界中西医结合杂志, 2019, 14(12): 1685-1690+1694.
[39] 王静, 李敏, 何立明, 等. 灯盏花素保护大鼠免受糖尿病肾病侵害的作用机制研究[J]. 世界中医药, 2022, 17(22): 3162-3167.
[40] Zhou, G., Cui, J., Xie, S., Wan, H., Luo, Y. and Guo, G. (2021) Vitexin, a Fenugreek Glycoside, Ameliorated Obesity-Induced Diabetic Nephropathy via Modulation of NF-κB/IkBα and AMPK/ACC Pathways in Mice. Bioscience, Biotechnology, and Biochemistry, 85, 1183-1193. [Google Scholar] [CrossRef] [PubMed]
[41] 申亮, 王培珍, 王鑫. 番泻叶苷A基于AMPK/Nox4信号通路对糖尿病肾病小鼠的作用[J]. 西北药学杂志, 2023, 38(4): 84-89.
[42] 蒋微, 蒋式骊, 刘平. 黄芪甲苷的药理作用研究进展[J]. 中华中医药学刊, 2019, 37(9): 2121-2124.
[43] 李国玲, 匡彬, 张舒, 等. 基于AMPK/eNOS信号通路探讨黄芪甲苷改善糖尿病肾病大鼠肾损伤的作用及机制研究[J]. 广州中医药大学学报, 2023, 40(3): 701-707.
[44] 郭亚莉, 刘青, 郭辉, 等. 山柰酚对链脲佐菌素诱导糖尿病肾病大鼠的治疗作用及机制研究[J]. 天然产物研究与开发, 2025, 37(3): 393-402.
[45] 苏蓓蓓, 杨丽霞, 梁永林, 等. 大黄糖络丸通过AMPK/mTOR/ULK1通路调控糖尿病肾病小鼠足细胞自噬的作用机制研究[J]. 中国临床药理学与治疗学, 2024, 29(3): 260-269.
[46] 王惠玲, 雷迪, 赵思阳, 等. 水陆地黄胶囊通过LKB1/AMPK/Sirt1信号通路调控糖尿病肾病大鼠足细胞自噬的实验研究[J]. 环球中医药, 2021, 14(12): 2142-2148.
[47] 刘春燕, 杨胜辉, 朱伟, 等. 金匮肾气汤促进糖尿病小鼠肾脏足细胞自噬[J]. 中国药理学通报, 2019, 35(3): 430-435.
[48] 童楠, 张宁. 中药益肾颗粒通过PI3k/Akt/mTOR和LKB1/AMPK/Sirt1信号通路对糖尿病肾病大鼠的干预作用研究[J]. 中华中医药杂志, 2018, 33(5): 1853-1857.
[49] 丁鑫, 顾悦, 王逸凡, 等. 加味当归补血汤对糖尿病肾病大鼠AMPK及PGC-1α的影响及相关作用机制[J]. 暨南大学学报(自然科学与医学版), 2023, 44(2): 147-156+185.
[50] 朱荔炜, 王春国, 洑晓哲, 等. 基于UHPLC-Q-Exactive Orbitrap MS和网络药理学探讨益气祛风方治疗糖尿病肾病作用机制[J]. 天津中医药, 2023, 40(11): 1466-1477.
[51] 王羲文, 赵进喜. 基于TLR4/MyD88/AMPK信号通路探索“从风论治”治法治疗糖尿病肾病的作用机制[J]. 环球中医药, 2023, 16(12): 2427-2433.
[52] 郭逸, 华川, 裴迅, 等. 玉泉丸对糖尿病肾病大鼠AMPK/FOXO3a通路及肾损伤的影响[J]. 中国中西医结合肾病杂志, 2021, 22(11): 954-958+1035.
[53] 陈霞, 彭文, 曹爱丽. 黄芪汤对糖尿病肾病小鼠AMPK-Camkkβ (LKB1)信号通路的影响[J]. 上海中医药大学学报, 2016, 30(5): 46-50.
[54] 郭燚, 唐比强, 赵娜, 等. 运脾和络方通过调控Sirt1/AMPK信号通路并激活自噬而减轻糖尿病肾损伤[J]. 中国病理生理杂志, 2019, 35(12): 2156-2162.