中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (4): 527-535.doi: 10.12092/j.issn.1009-2501.2026.04.012
孙立亚(
), 李嘉鑫, 孙贵炎, 陈志超, 王庆峰, 杨宇峰(), 石岩
收稿日期:2025-05-18
修回日期:2025-07-08
出版日期:2026-04-26
发布日期:2026-04-30
通讯作者:
杨宇峰
E-mail:952762386@qq.com;Yangyufeng5698@163.com
作者简介:孙立亚，女，博士，从事内分泌疾病的中医内科学基础与临床研究。E-mail：基金资助:
Liya SUN(), Jiaxin LI, Guiyan SUN, Zhichao CHEN, Qingfeng WANG, Yufeng YANG(), Yan SHI
Received:2025-05-18
Revised:2025-07-08
Online:2026-04-26
Published:2026-04-30
Contact:
Yufeng YANG
E-mail:952762386@qq.com;Yangyufeng5698@163.com
摘要：
糖尿病肾病以肾小球滤过进行性受损和高血糖水平，进而导致终末期肾功能衰竭为特征，是全球终末期肾病的主要原因。肠道菌群在糖尿病肾病中起着重要作用，支链氨基酸是肠道菌群的代谢产物，也是能量支持、营养感应、神经递质合成和细胞信号传导的关键调节因子，是糖尿病肾病发生的关键生物标志物。中医药可通过改善肠道菌群功能，维持其平衡稳态，减轻支链氨基酸代谢紊乱而达到防治糖尿病肾病的目的。本文主要探讨肠道菌群和支链氨基酸在糖尿病肾病中的作用以及中医药通过调节肠道菌群和支链氨基酸代谢防治糖尿病肾病的研究进展，以期为糖尿病肾病的防治提供具有中医特色的新思路。
中图分类号:
孙立亚, 李嘉鑫, 孙贵炎, 陈志超, 王庆峰, 杨宇峰, 石岩. 基于肠道菌群和支链氨基酸探讨中医药防治糖尿病肾病的研究进展[J]. 中国临床药理学与治疗学, 2026, 31(4): 527-535.
Liya SUN, Jiaxin LI, Guiyan SUN, Zhichao CHEN, Qingfeng WANG, Yufeng YANG, Yan SHI. Research progress of traditional Chinese medicine in the prevention and treatment of diabetic nephropathy based on intestinal flora and branched-chain amino acids[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 527-535.
图 1
Fig.1 Mechanisms linking gut microbiota dysbiosis and BCAAs dysregulation in diabetic nephropathy progression
| 1 |
He Y, Zhang H, Yang Y, et al. Using metabolomics in diabetes management with traditional Chinese medicine: A review[J]. Am J Chin Med, 2021, 49 (8): 1813- 1837.
doi: 10.1142/S0192415X21500865 |
| 2 |
Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract, 2022, 183, 109119.
doi: 10.1016/j.diabres.2021.109119 |
| 3 |
Saeedi P, Salpea P, Karuranga S, et al. Mortality attributable to diabetes in 20-79 years old adults, 2019 estimates: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition[J]. Diabetes Res Clin Pract, 2020, 162, 108086.
doi: 10.1016/j.diabres.2020.108086 |
| 4 |
Zhu T, Goodarzi MO. Metabolites linking the gut microbiome with risk for type 2 diabetes[J]. Curr Nutr Rep, 2020, 9 (2): 83- 93.
doi: 10.1007/s13668-020-00307-3 |
| 5 |
Sikalidis AK, Maykish A. The gut microbiome and type 2 diabetes mellitus: Discussing a complex relationship[J]. Biomedicines, 2020, 8 (1): 8.
doi: 10.3390/biomedicines8010008 |
| 6 | 郭天灏, 程海波. 肠道菌群与氨基酸代谢的相互作用研究进展[J]. 中华中医药杂志, 2023, 38 (10): 4851- 4857. |
| 7 |
Tao S, Li L, Li L, et al. Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition[J]. Acta Diabetol, 2019, 56 (5): 581- 592.
doi: 10.1007/s00592-019-01316-7 |
| 8 |
Asghari G, Farhadnejad H, Teymoori F, et al. High dietary intake of branched-chain amino acids is associated with an increased risk of insulin resistance in adults[J]. J Diabetes, 2018, 10 (5): 357- 364.
doi: 10.1111/1753-0407.12639 |
| 9 |
Anderson JR, Carroll I, Azcarate-Peril MA, et al. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults[J]. Sleep Med, 2017, 38, 104- 107.
doi: 10.1016/j.sleep.2017.07.018 |
| 10 |
Cheng G, Liu Y, Guo R, et al. Molecular mechanisms of gut microbiota in diabetic nephropathy[J]. Diabetes Res Clin Pract, 2024, 213, 111726.
doi: 10.1016/j.diabres.2024.111726 |
| 11 |
He L, Yang FQ, Tang P, et al. Regulation of the intestinal flora: A potential mechanism of natural medicines in the treatment of type 2 diabetes mellitus[J]. Biomed Pharmacother, 2022, 151, 113091.
doi: 10.1016/j.biopha.2022.113091 |
| 12 |
Li Q, Chang Y, Zhang K, et al. Implication of the gut microbiome composition of type 2 diabetic patients from northern China[J]. Sci Rep, 2020, 10 (1): 5450.
doi: 10.1038/s41598-020-62224-3 |
| 13 |
Tian E, Wang F, Zhao L, et al. The pathogenic role of intestinal flora metabolites in diabetic nephropathy[J]. Front Physiol, 2023, 14, 1231621.
doi: 10.3389/fphys.2023.1231621 |
| 14 |
Du X, Liu J, Xue Y, et al. Alteration of gut microbial profile in patients with diabetic nephropathy[J]. Endocrine, 2021, 73 (1): 71- 84.
doi: 10.1007/s12020-021-02721-1 |
| 15 |
Lu J, Chen PP, Zhang JX, et al. GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity[J]. Theranostics, 2021, 11 (10): 4728- 4742.
doi: 10.7150/thno.56598 |
| 16 |
Lu CC, Hu ZB, Wang R, et al. Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy[J]. Acta Pharmacol Sin, 2020, 41 (8): 1111- 1118.
doi: 10.1038/s41401-019-0326-5 |
| 17 |
Fiaccadori E, Cosola C, Sabatino A. Targeting the gut for early diagnosis, prevention, and cure of diabetic kidney disease: Is the phenyl sulfate story another step forward ?[J]. Am J Kidney Dis, 2020, 75 (1): 144- 147.
doi: 10.1053/j.ajkd.2019.07.001 |
| 18 |
Wang P, Guo R, Bai X, et al. Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice[J]. Front Endocrinol (Lausanne), 2022, 13, 1034818.
doi: 10.3389/fendo.2022.1034818 |
| 19 |
Pengrattanachot N, Thongnak L, Lungkaphin A. The impact of prebiotic fructooligosaccharides on gut dysbiosis and inflammation in obesity and diabetes related kidney disease[J]. Food Funct, 2022, 13 (11): 5925- 5945.
doi: 10.1039/D1FO04428A |
| 20 |
Dai Y, Quan J, Xiong L, et al. Probiotics improve renal function, glucose, lipids, inflammation and oxidative stress in diabetic kidney disease: a systematic review and meta-analysis[J]. Ren Fail, 2022, 44 (1): 862- 880.
doi: 10.1080/0886022X.2022.2079522 |
| 21 |
Li YJ, Chen X, Kwan TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid-mediated activation of G protein-coupled receptors GPR43 and GPR109A[J]. J Am Soc Nephrol, 2020, 31 (6): 1267- 1281.
doi: 10.1681/ASN.2019101029 |
| 22 |
Zhang Y, Zhan L, Zhang L, et al. Branched-chain amino acids in liver diseases: Complexity and controversy[J]. Nutrients, 2024, 16 (12): 1875.
doi: 10.3390/nu16121875 |
| 23 |
Kaspy MS, Hannaian SJ, Bell ZW, et al. The effects of branched-chain amino acids on muscle protein synthesis, muscle protein breakdown and associated molecular signalling responses in humans: an update[J]. Nutr Res Rev, 2024, 37 (2): 273- 286.
doi: 10.1017/S0954422423000197 |
| 24 |
Jin Q, Ma R. Metabolomics in diabetes and diabetic complications: insights from Epidemiological Studies[J]. Cells, 2021, 10 (11): 2832.
doi: 10.3390/cells10112832 |
| 25 |
Deng X, Tang C, Fang T, et al. Disruption of branched-chain amino acid homeostasis promotes the progression of DKD via enhancing inflammation and fibrosis-associated epithelial-mesenchymal transition[J]. Metabolism, 2025, 162, 156037.
doi: 10.1016/j.metabol.2024.156037 |
| 26 |
Liu S, Li L, Lou P, et al. Elevated branched-chain α-keto acids exacerbate macrophage oxidative stress and chronic inflammatory damage in type 2 diabetes mellitus[J]. Free Radic Biol Med, 2021, 175, 141- 154.
doi: 10.1016/j.freeradbiomed.2021.08.240 |
| 27 |
Zhenyukh O, González-Amor M, Rodrigues-Diez RR, et al. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation[J]. J Cell Mol Med, 2018, 22 (10): 4948- 4962.
doi: 10.1111/jcmm.13759 |
| 28 | Wang Y, Li X, Zhang H, et al. Branched-chain amino acid catabolism deficiency accelerates diabetic kidney disease via activating mTORC1 signaling[J]. Kidney Int, 2022, 102 (4): 897- 911. |
| 29 |
Yu D, Richardson NE, Green CL, et al. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine[J]. Cell Metab, 2021, 33 (5): 905- 922.
doi: 10.1016/j.cmet.2021.03.025 |
| 30 |
Zhao H, Zhang F, Sun D, et al. Branched-chain amino acids exacerbate obesity-related hepatic glucose and lipid metabolic disorders via attenuating Akt2 signaling[J]. Diabetes, 2020, 69 (6): 1164- 1177.
doi: 10.2337/db19-0920 |
| 31 |
Dimou A, Tsimihodimos V, Bairaktari E. The critical role of the branched chain amino acids (BCAAs) catabolism-regulating enzymes, branched-chain aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), in human pathophysiology[J]. Int J Mol Sci, 2022, 23 (7): 4022.
doi: 10.3390/ijms23074022 |
| 32 |
Zhang L, Yue Y, Shi M, et al. Dietary Luffa cylindrica (L. ) Roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice[J]. Food Chem, 2020, 320, 126648.
doi: 10.1016/j.foodchem.2020.126648 |
| 33 |
Pillai SM, Herzog B, Seebeck P, et al. Differential impact of dietary branched chain and aromatic amino acids on chronic kidney disease progression in rats[J]. Front Physiol, 2019, 10, 1460.
doi: 10.3389/fphys.2019.01460 |
| 34 |
Mi N, Zhang XJ, Ding Y, et al. Branched-chain amino acids attenuate early kidney injury in diabetic rats[J]. Biochem Biophys Res Commun, 2015, 466 (2): 240- 246.
doi: 10.1016/j.bbrc.2015.09.017 |
| 35 |
Zhou C, Zhang Q, Lu L, et al. Metabolomic profiling of amino acids in human plasma distinguishes diabetic kidney disease from type 2 diabetes mellitus[J]. Front Med (Lausanne), 2021, 8, 765873.
doi: 10.3389/fmed.2021.765873 |
| 36 |
Kim JE, Nam H, Park JI, et al. Gut microbial genes and metabolism for methionine and branched-chain amino acids in diabetic nephropathy[J]. Microbiol Spectr, 2023, 11 (2): e234422.
doi: 10.1128/spectrum.02344-22 |
| 37 |
Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity[J]. Nature, 2016, 535 (7612): 376- 381.
doi: 10.1038/nature18646 |
| 38 |
Nie Q, Hu J, Gao H, et al. Bioactive dietary fibers selectively promote gut microbiota to exert antidiabetic effects[J]. J Agric Food Chem, 2021, 69 (25): 7000- 7015.
doi: 10.1021/acs.jafc.1c01465 |
| 39 |
Li WZ, Stirling K, Yang JJ, et al. Gut microbiota and diabetes: From correlation to causality and mechanism[J]. World J Diabetes, 2020, 11 (7): 293- 308.
doi: 10.4239/wjd.v11.i7.293 |
| 40 | Bloomgarden Z. Diabetes and branched-chain amino acids: What is the link ?[J]. J Diabetes, 2018, 10 (5): 350- 352. |
| 41 |
Yang J, Dong H, Wang Y, et al. Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis[J]. Int J Biol Macromol, 2020, 163, 442- 456.
doi: 10.1016/j.ijbiomac.2020.06.153 |
| 42 |
罗欣杰, 杨建华, 胡君萍. 肉苁蓉多糖通过影响肠道菌群抑制Toll样受体4/核因子-κB途径改善小鼠糖尿病肾病[J]. 食品科学, 2024, 45 (21): 185- 193.
doi: 10.7506/spkx1002-6630-20240416-154 |
| 43 |
Wang F, Liu C, Ren L, et al. Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway[J]. Pharm Biol, 2023, 61 (1): 427- 436.
doi: 10.1080/13880209.2023.2174145 |
| 44 |
Zhou K, Zhang J, Liu C, et al. Sanziguben polysaccharides inhibit diabetic nephropathy through NF-κB-mediated anti-inflammation[J]. Nutr Metab (Lond), 2021, 18 (1): 81.
doi: 10.1186/s12986-021-00601-z |
| 45 |
Lyu X, Zhang TT, Ye Z, et al. Astragaloside IV mitigated diabetic nephropathy by restructuring intestinal microflora and ferroptosis[J]. Mol Nutr Food Res, 2024, 68 (6): e2300734.
doi: 10.1002/mnfr.202300734 |
| 46 |
于晓依, 常畅, 陈天笑, 等. 王不留行黄酮苷改善糖尿病肾病小鼠肠道菌群紊乱和肾脏脂质沉积的研究[J]. 华西药学杂志, 2024, 39 (1): 36- 42.
doi: 10.13375/j.cnki.wcjps.2024.01.008 |
| 47 |
Ju CG, Zhu L, Wang W, et al. Cornus officinalis prior and post-processing: Regulatory effects on intestinal flora of diabetic nephropathy rats[J]. Front Pharmacol, 2022, 13, 1039711.
doi: 10.3389/fphar.2022.1039711 |
| 48 |
Han C, Shen Z, Cui T, et al. Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis"[J]. J Ethnopharmacol, 2023, 307, 116257.
doi: 10.1016/j.jep.2023.116257 |
| 49 |
姚宇剑, 武素, 倪雅丽, 等. 缩泉益肾方对db-/db-小鼠的肠道菌群影响的研究[J]. 时珍国医国药, 2022, 33 (2): 291- 294.
doi: 10.3969/j.issn.1008-0805.2022.02.09 |
| 50 | 姚宇剑, 倪雅丽, 李想, 等. 缩泉益肾方对糖尿病肾病小鼠肠道菌群多样性的影响[J]. 时珍国医国药, 2020, 31 (8): 1846- 1848. |
| 51 |
杨超茅, 张顺宵, 李园园, 等. 六味地黄汤加减联合氯沙坦钾对糖尿病肾病大鼠ACE1/AngⅡ/AT1R轴及肠道菌群的影响[J]. 中国实验方剂学杂志, 2024, 30 (6): 1- 9.
doi: 10.13422/j.cnki.syfjx.20232122 |
| 52 |
Zhang CY, Yue DJ, Wang D, et al. Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease[J]. Front Pharmacol, 2024, 15, 1346168.
doi: 10.3389/fphar.2024.1346168 |
| 53 |
Rong G, Weng W, Huang J, et al. Artemether alleviates diabetic kidney disease by modulating amino acid metabolism[J]. Biomed Res Int, 2022, 2022, 7339611.
doi: 10.1155/2022/7339611 |
| 54 |
Chen R, Liao C, Guo Q, et al. Combined systems pharmacology and fecal metabonomics to study the biomarkers and therapeutic mechanism of type 2 diabetic nephropathy treated with Astragalus and Leech[J]. RSC Adv, 2018, 8 (48): 27448- 27463.
doi: 10.1039/C8RA04358B |
| 55 |
Liu Y, Chen X, Liu Y, et al. Metabolomic study of the protective effect of Gandi capsule for diabetic nephropathy[J]. Chem Biol Interact, 2019, 314, 108815.
doi: 10.1016/j.cbi.2019.108815 |
| 56 |
Shi R, Tao Y, Tang H, et al. Abelmoschus manihot ameliorates the levels of circulating metabolites in diabetic nephropathy by modulating gut microbiota in non-obese diabetes mice[J]. Microb Biotechnol, 2023, 16 (4): 813- 826.
doi: 10.1111/1751-7915.14200 |
| 57 |
Shao J, Liu Y, Wang H, et al. An integrated fecal microbiome and metabolomics in T2DM rats reveal antidiabetes effects from host-microbial metabolic axis of EtOAc extract from sophora flavescens[J]. Oxid Med Cell Longev, 2020, 2020, 1805418.
doi: 10.1155/2020/1805418 |
| 58 |
Yue SJ, Liu J, Wang AT, et al. Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids[J]. Am J Physiol Endocrinol Metab, 2019, 316 (1): E73- E85.
doi: 10.1152/ajpendo.00256.2018 |
| 59 | Zheng XX, Li DX, Li YT, et al. Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota-host co-metabolism of branched-chain amino acid[J]. Phytother Res, 2023, 37 (8): 3195- 3210. |
| 60 |
Bao M, Hou K, Xin C, et al. Portulaca oleracea L. extract alleviated type 2 diabetes via modulating the gut microbiota and serum branched-chain amino acid metabolism[J]. Mol Nutr Food Res, 2022, 66 (11): e2101030.
doi: 10.1002/mnfr.202101030 |
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