基于“肠肾轴”理论探讨肠道菌群紊乱对糖尿病肾病的影响及中医治疗
Discussion on the Influence of Intestinal Flora Disturbance on Diabetic Nephropathy and the Treatment of Traditional Chinese Medicine Based on the Theory of “Entero-Renal Axis”
DOI: 10.12677/tcm.2024.139361, PDF,   
作者: 张阳阳:黑龙江中医药大学研究生院,黑龙江 哈尔滨;栾仲秋:黑龙江中医药大学附属第一医院肾病一科,黑龙江 哈尔滨
关键词: 糖尿病肾病肠肾轴肠道菌群中医药Diabetic Kidney Disease Intestine-Kidney Axis Gut Microbiota Traditional Chinese Medicine
摘要: 糖尿病肾病(DKD)是我国常见的慢性代谢性疾病,近些年来患病率仍在逐步上升,已成为全球性公共健康问题。肠道作为人体第二大器官,随着对肠道与肾脏之间关系的深入研究,“肠肾轴”逐渐成为研究热点。近年诸多研究表明,DKD患者肠道菌群与健康人存在明显差异,肠道菌群及其代谢产物紊乱可导致肠道通透性改变、过度激活肾素–血管紧张素–醛固酮系统(RAAS)及全身慢性微炎症状态等加重DKD的发生发展。中医药在治疗DKD患者方面展现出效果良好、副作用小、治疗途径广泛等优势,并在此过程中发挥了重要作用。本文基于“肠肾轴”理论,对肠道菌群与DKD之间的关系及中医治疗进行论述,以期为DKD治疗提供参考。
Abstract: Diabetic nephropathy (DKD) is a common chronic metabolic disease in China. In recent years, the prevalence rate has been increasing gradually, and it has become a global public health problem. The intestinal tract is the second largest organ in human body, with the in-depth study of the relationship between the intestinal tract and kidney, “enterorenal axis” has gradually become a research hotspot. In recent years, many studies have shown that the intestinal flora of DKD patients is significantly different from that of healthy people, and the disturbance of intestinal flora and its metabolites can lead to changes in intestinal permeability, excessive activation of renin-angiotensin-aldosterone system (RAAS) and chronic systemic microinflammation, which can aggravate the occurrence and development of DKD. Traditional Chinese medicine plays an important role in the treatment of DKD patients with good effect, small side effects, wide treatment channels and other advantages. Based on the theory of “entero-renal axis”, this paper discusses the relationship between intestinal flora and DKD and the treatment of TCM, in order to provide a reference for the treatment of DKD.
文章引用:张阳阳, 栾仲秋. 基于“肠肾轴”理论探讨肠道菌群紊乱对糖尿病肾病的影响及中医治疗[J]. 中医学, 2024, 13(9): 2435-2443. https://doi.org/10.12677/tcm.2024.139361

参考文献

[1] GBD Chronic Kidney Disease Collaboration (2020) Global, Regional, and National Burden of Chronic Kidney Disease, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet, 395, 709-733.
[2] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版) (上) [J]. 中国实用内科杂志, 2021, 41(8): 668-695.
[3] 王慧玲, 黄国东, 陈宇, 等. 基于肠道菌群探讨从中医脾胃论治糖尿病肾病[J]. 中医学报, 2024, 39(7): 1374-1383.
[4] Ritz, E. (2011) Intestinal-Renal Syndrome: Mirage or Reality? Blood Purification, 31, 70-76. [Google Scholar] [CrossRef] [PubMed]
[5] Meijers, B.K.I. and Evenepoel, P. (2011) The Gut-Kidney Axis: Indoxyl Sulfate, P-Cresyl Sulfate and CKD Progression. Nephrology Dialysis Transplantation, 26, 759-761. [Google Scholar] [CrossRef] [PubMed]
[6] 谢珊. 肠道菌群结构变化与慢性肾功能衰竭发展关系的研究[D]: [博士学位论文]. 广州: 南方医科大学, 2014.
[7] 徐蕾, 马晓燕. 基于“肠-肾轴”理论治疗慢性肾脏病研究进展[J]. 陕西中医药大学学报, 2022, 45(3): 114-119.
[8] 中华中医药学会. ZYYXH/T 3. 3-2007 糖尿病肾病[S]. 北京: 中国中医药出版社, 2007.
[9] 殷松江, 盛梅笑. 基于肠肾轴概念谈通腑泄浊法在慢性肾脏病治疗中的应用[J]. 中国临床研究, 2016, 29(3): 417-419.
[10] Ramezani, A., Massy, Z.A., Meijers, B., Evenepoel, P., Vanholder, R. and Raj, D.S. (2016) Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. American Journal of Kidney Diseases, 67, 483-498. [Google Scholar] [CrossRef] [PubMed]
[11] Hooper, L.V., Littman, D.R. and Macpherson, A.J. (2012) Interactions between the Microbiota and the Immune System. Science, 336, 1268-1273. [Google Scholar] [CrossRef] [PubMed]
[12] Letchumanan, G., Abdullah, N., Marlini, M., Baharom, N., Lawley, B., Omar, M.R., et al. (2022) Gut Microbiota Composition in Prediabetes and Newly Diagnosed Type 2 Diabetes: A Systematic Review of Observational Studies. Frontiers in Cellular and Infection Microbiology, 12, Article 943427. [Google Scholar] [CrossRef] [PubMed]
[13] Rackaityte, E. and Lynch, S.V. (2018) Rules of Engagement in the Gut Microbiome. Nature Medicine, 24, 1642-1644. [Google Scholar] [CrossRef] [PubMed]
[14] Said, I., Ahad, H. and Said, A. (2022) Gut Microbiome in Non-Alcoholic Fatty Liver Disease Associated Hepatocellular Carcinoma: Current Knowledge and Potential for Therapeutics. World Journal of Gastrointestinal Oncology, 14, 947-958. [Google Scholar] [CrossRef] [PubMed]
[15] 冯春念, 曾琳智, 王仕均, 等. 2型糖尿病与糖尿病肾病患者微炎症及肠道微生物多样性分析[J]. 中国微生态学杂志, 2020, 32(11): 1273-1278.
[16] Del Chierico, F., Rapini, N., Deodati, A., Matteoli, M.C., Cianfarani, S. and Putignani, L. (2022) Pathophysiology of Type 1 Diabetes and Gut Microbiota Role. International Journal of Molecular Sciences, 23, Article 14650. [Google Scholar] [CrossRef] [PubMed]
[17] Afsar, B., Vaziri, N.D., Aslan, G., Tarim, K. and Kanbay, M. (2016) Gut Hormones and Gut Microbiota: Implications for Kidney Function and Hypertension. Journal of the American Society of Hypertension, 10, 954-961. [Google Scholar] [CrossRef] [PubMed]
[18] Du, X., Liu, J., Xue, Y., Kong, X., Lv, C., Li, Z., et al. (2021) Alteration of Gut Microbial Profile in Patients with Diabetic Nephropathy. Endocrine, 73, 71-84. [Google Scholar] [CrossRef] [PubMed]
[19] Zhang, L., Lu, Q.Y., Wu, H., Cheng, Y.L., Kang, J. and Xu, Z.G. (2023) The Intestinal Microbiota Composition in Early and Late Stages of Diabetic Kidney Disease. Microbiology Spectrum, 11, e0038223.
[20] 孙雅娴. 早期肾功改变的2型糖尿病患者肠道菌群分析研究[D]: [硕士学位论文]. 大连: 大连医科大学, 2016.
[21] American Diabetes Association (2019) 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care, 43, S14-S31. [Google Scholar] [CrossRef] [PubMed]
[22] 王淑亮, 苏永峰. 肠道菌群在2型糖尿病中的研究进展[J]. 临床荟萃, 2024, 39(3): 274-278.
[23] Craciun, C., Neag, M., Catinean, A., Mitre, A., Rusu, A., Bala, C., et al. (2022) The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus. Biomedicines, 10, Article 308. [Google Scholar] [CrossRef] [PubMed]
[24] Zeng, J.Y., Wang, Y., Miao, M. and Bao, X.R. (2021) The Effects of Rhubarb for the Treatment of Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis. Frontiers in Pharmacology, 12, Article 602816.
[25] 李洪梅, 朱海清. 中国糖尿病肾脏病防治指南(2021年版)解读[J]. 中国医刊, 2022, 57(2): 133-138.
[26] Moratal, C., Laurain, A., Naïmi, M., Florin, T., Esnault, V., Neels, J.G., et al. (2021) Regulation of Monocytes/macrophages by the Renin-Angiotensin System in Diabetic Nephropathy: State of the Art and Results of a Pilot Study. International Journal of Molecular Sciences, 22, Article 6009. [Google Scholar] [CrossRef] [PubMed]
[27] 潘道延, 沈洁. 肾素-血管紧张素-醛固酮系统与糖尿病肾病[J]. 中华临床医师杂志(电子版), 2015, 9(4): 523-527.
[28] Lu, C.C., Ma, K.L., Ruan, X.Z. and Liu, B.C. (2018) Intestinal Dysbiosis Activates Renal Renin-Angiotensin System Contributing to Incipient Diabetic Nephropathy. International Journal of Medical Sciences, 15, 816-822. [Google Scholar] [CrossRef] [PubMed]
[29] Machado, A.S., Oliveira, J.R., Lelis, D.D.F., de Paula, A.M.B., Guimarães, A.L.S., Andrade, J.M.O., et al. (2020) Oral Probiotic Bifidobacterium Longum Supplementation Improves Metabolic Parameters and Alters the Expression of the Renin-Angiotensin System in Obese Mice Liver. Biological Research for Nursing, 23, 100-108. [Google Scholar] [CrossRef] [PubMed]
[30] 邢盼盼, 刘萍, 王俊平. 肠道通透性相关疾病及其影响因素的研究进展[J]. 中华全科医师杂志, 2017, 16(4): 320-323.
[31] Wang, S., Shao, B., Zhao, S., Fang, J., Gu, L., Miao, C., et al. (2018) Impact of Paneth Cell Autophagy on Inflammatory Bowel Disease. Frontiers in Immunology, 9, Article 693. [Google Scholar] [CrossRef] [PubMed]
[32] Monaco, A., Ovryn, B., Axis, J. and Amsler, K. (2021) The Epithelial Cell Leak Pathway. International Journal of Molecular Sciences, 22, Article 7677. [Google Scholar] [CrossRef] [PubMed]
[33] 吴雅茹, 魏凯悦, 王彩丽. 肠道菌群失衡与肠道屏障损伤在糖尿病肾脏疾病中的研究进展[J]. 肾脏病与透析肾移植杂志, 2023, 32(5): 477-480, 454.
[34] Fu, X., Liu, Z., Zhu, C., Mou, H. and Kong, Q. (2018) Nondigestible Carbohydrates, Butyrate, and Butyrate-Producing Bacteria. Critical Reviews in Food Science and Nutrition, 59, S130-S152. [Google Scholar] [CrossRef] [PubMed]
[35] Gonzalez, A., Krieg, R., Massey, H.D., Carl, D., Ghosh, S., Gehr, T.W.B., et al. (2018) Sodium Butyrate Ameliorates Insulin Resistance and Renal Failure in CKD Rats by Modulating Intestinal Permeability and Mucin Expression. Nephrology Dialysis Transplantation, 34, 783-794. [Google Scholar] [CrossRef] [PubMed]
[36] Zhong, C., Bai, X., Chen, Q., Ma, Y., Li, J., Zhang, J., et al. (2022) Gut Microbial Products Valerate and Caproate Predict Renal Outcome among the Patients with Biopsy-Confirmed Diabetic Nephropathy. Acta Diabetologica, 59, 1469-1477. [Google Scholar] [CrossRef] [PubMed]
[37] van der Hee, B. and Wells, J.M. (2021) Microbial Regulation of Host Physiology by Short-Chain Fatty Acids. Trends in Microbiology, 29, 700-712. [Google Scholar] [CrossRef] [PubMed]
[38] Lavelle, A. and Sokol, H. (2020) Gut Microbiota-Derived Metabolites as Key Actors in Inflammatory Bowel Disease. Nature Reviews Gastroenterology & Hepatology, 17, 223-237. [Google Scholar] [CrossRef] [PubMed]
[39] 平易, 魏艳玲, 陈东风, 等. 肠道短链脂肪酸与肠黏膜屏障[J]. 胃肠病学和肝病学杂志, 2022, 31(5): 508-512.
[40] Drucker, D.J. (2018) Mechanisms of Action and Therapeutic Application of Glucagon-Like Peptide-1. Cell Metabolism, 27, 740-756. [Google Scholar] [CrossRef] [PubMed]
[41] 孙静, 张帆. 2型糖尿病患者血糖控制状态与肠道微生态、短链脂肪酸、D-乳酸、免疫细胞水平的相关分析[J]. 临床内科杂志, 2024, 41(6): 408-410.
[42] 夏西茜, 丁珂珂, 张慧恒, 等. 肠道菌群介导胆汁酸影响炎症性肠病的研究进展[J]. 上海交通大学学报(医学版), 2024, 44(7): 839-846.
[43] Song, Z., Cai, Y., Lao, X., Wang, X., Lin, X., Cui, Y., et al. (2019) Taxonomic Profiling and Populational Patterns of Bacterial Bile Salt Hydrolase (BSH) Genes Based on Worldwide Human Gut Microbiome. Microbiome, 7, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[44] 潘婷. 基于肠道菌群-胆汁酸代谢探讨“调脏通络”电针治疗2型糖尿病的效应与机制[D]: [博士学位论文]. 长春: 长春中医药大学, 2023.
[45] Wang, X.X., Wang, D., Luo, Y., Myakala, K., Dobrinskikh, E., Rosenberg, A.Z., et al. (2017) FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity. Journal of the American Society of Nephrology, 29, 118-137. [Google Scholar] [CrossRef] [PubMed]
[46] 杨波, 熊婉媛, 蔡小玲, 等. 肠源性氧化三甲胺在慢性肾病中的作用[J]. 生命科学, 2018, 30(5): 580-584.
[47] Dambrova, M., Latkovskis, G., Kuka, J., Strele, I., Konrade, I., Grinberga, S., et al. (2016) Diabetes Is Associated with Higher Trimethylamine N-Oxide Plasma Levels. Experimental and Clinical Endocrinology & Diabetes, 124, 251-256. [Google Scholar] [CrossRef] [PubMed]
[48] Wang, Z., Bergeron, N., Levison, B.S., Li, X.S., Chiu, S., Jia, X., et al. (2018) Impact of Chronic Dietary Red Meat, White Meat, or Non-Meat Protein on Trimethylamine N-Oxide Metabolism and Renal Excretion in Healthy Men and Women. European Heart Journal, 40, 583-594. [Google Scholar] [CrossRef] [PubMed]
[49] 孙田, 李琳, 雒否乐. 糖尿病肾病患者血清三甲胺、氧化三甲胺及其比值与肾损伤的相关性分析[J]. 临床内科杂志, 2020, 37(9): 659-660.
[50] 杨柳. 氧化三甲胺对慢性肾脏病的影响和对策[J].肾脏病与透析肾移植杂志, 2019, 28(5): 474-478.
[51] Ke, Y., Li, D., Zhao, M., Liu, C., Liu, J., Zeng, A., et al. (2018) Gut Flora-Dependent Metabolite Trimethylamine-N-Oxide Accelerates Endothelial Cell Senescence and Vascular Aging through Oxidative Stress. Free Radical Biology and Medicine, 116, 88-100. [Google Scholar] [CrossRef] [PubMed]
[52] 焦书沛, 姜晨. “肠-肾轴”理论研究现状及分析[J]. 中国中西医结合肾病杂志, 2017, 18(7): 656-658.
[53] 吕仁和, 赵进喜, 王越. 糖尿病肾病临床研究述评[J]. 北京中医药大学学报, 1994(2): 2-6, 72.
[54] 张文杰, 赖星海, 陈佳薇. 山药多糖治疗肥胖糖尿病肾病大鼠的效果观察及对其肾功能和肠道微生态的影响[J]. 中国微生态学杂志, 2021, 33(1): 37-42.
[55] 徐卓, 项想, 尚尔鑫, 等. 丹参茎叶总酚酸对2型糖尿病肾病小鼠肠道菌群和短链脂肪酸的调节作用[J]. 药学学报, 2021, 56(4): 1035-1048.
[56] 杜小梅, 潘薇, 梁颖兰, 等. 参芪地黄汤加减治疗气阴两虚型糖尿病肾病疗效观察及对肠道菌群和炎症因子的影响[J]. 中药新药与临床药理, 2021, 32(4): 566-572.
[57] 陈茜, 李凯利, 郝拥玲, 等. 糖肾灌肠方治疗早期糖尿病肾病的随机对照研究[J]. 新疆中医药, 2014, 32(4): 5-8.
[58] 朱娟, 李凯利, 杨苏秀. 中医外治法治疗糖尿病肾病研究进展[J]. 新疆中医药, 2015, 33(5): 97-100.