短链脂肪酸在中医药治疗2型糖尿病伴代谢相关脂肪性肝病的研究进展
Research Progress on Short-Chain Fatty Acids in the Treatment of Type 2 Diabetes Mellitus Complicated with Metabolic-Associated Fatty Liver Disease by Traditional Chinese Medicine
DOI: 10.12677/tcm.2026.158418, PDF,   
作者: 孙 梦：黑龙江中医药大学研究生院，黑龙江 哈尔滨；田 源*：黑龙江中医药大学附属第三医院内分泌科，黑龙江 哈尔滨
关键词: 代谢相关脂肪性肝病；2型糖尿病；短链脂肪酸；中医药；Metabolic-Associated Fatty Liver Disease； Type 2 Diabetes Mellitus； Short-Chain Fatty Acids； Traditional Chinese Medicine
摘要: 2型糖尿病(T2DM)是一种以胰岛素的相对缺乏导致高血糖状态为主要特征的代谢性疾病。代谢相关脂肪性肝病(MAFLD)是一种以肝细胞脂质过度沉积为特征的多系统慢性肝损伤疾病。本研究旨在系统梳理短链脂肪酸(SCFAs)调控T2DM伴MAFLD的分子通路，总结中医药通过调控SCFAs防治共病的研究证据，弥补现代医学缺乏靶向药物的临床短板。采用文献系统综述法，整合SCFAs代谢机制、中药复方与单体活性成分相关动物、细胞及临床试验数据及结果。以期为临床消渴合并肝瘅精准辨证用药、开发肠道靶向中药制剂提供理论依据。现有研究存在机制链条不完整等局限，后续需完善多维度验证。
Abstract: Type 2 diabetes mellitus (T2DM) is a metabolic disorder mainly characterized by hyperglycemia caused by relative insulin deficiency. Metabolic-associated fatty liver disease (MAFLD) is a multisystem chronic liver injury disorder marked by excessive lipid deposition in hepatocytes. This study systematically sorts out the molecular pathways through which short-chain fatty acids (SCFAs) regulate T2DM combined with MAFLD, and summarizes research evidence that traditional Chinese medicine (TCM) prevents and treats this comorbidity by modulating SCFAs, so as to make up for the clinical deficiency of targeted therapeutic drugs in modern medicine. A systematic literature review method was adopted to integrate metabolic mechanisms of SCFAs, as well as data and findings from animal, cellular and clinical trials related to TCM compound formulas and monomer active ingredients. It is expected to provide theoretical basis for precise syndrome differentiation and medication for clinical Xiaoke Disease combined with Gandan, and the development of intestinal-targeted TCM preparations. Existing studies have limitations such as incomplete mechanistic chains, and multi-dimensional verification should be supplemented in follow-up research.
文章引用：孙梦, 田源. 短链脂肪酸在中医药治疗2型糖尿病伴代谢相关脂肪性肝病的研究进展[J]. 中医学, 2026, 15(8): 141-148. https://doi.org/10.12677/tcm.2026.158418

参考文献

[1] Colagiuri, S. and Ceriello, A. (2025) 7. Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Type 2 Diabetes. Diabetes Research and Clinical Practice, 222, Article ID: 112151.
https://doi.org/10.1016/j.diabres.2025.112151
[2] Cusi, K., Abdelmalek, M.F., Apovian, C.M., Balapattabi, K., Bannuru, R.R., Barb, D., et al. (2025) Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in People with Diabetes: The Need for Screening and Early Intervention. A Consensus Report of the American Diabetes Association. Diabetes Care, 48, 1057-1082.
https://doi.org/10.2337/dci24-0094
[3] Huang, D.Q., Noureddin, N., Ajmera, V., Amangurbanova, M., Bettencourt, R., Truong, E., et al. (2023) Type 2 Diabetes, Hepatic Decompensation, and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: An Individual Participant-Level Data Meta-Analysis. The Lancet Gastroenterology & Hepatology, 8, 829-836.
https://doi.org/10.1016/s2468-1253(23)00157-7
[4] WHO CVD Risk Chart Working Group (2019) World Health Organization Cardiovascular Disease Risk Charts: Revised Models to Estimate Risk in 21 Global Regions. The Lancet Global Health, 7, e1332-e1345.
[5] Targher, G., Chonchol, M., Bertolini, L., Rodella, S., Zenari, L., Lippi, G., et al. (2008) Increased Risk of CKD among Type 2 Diabetics with Nonalcoholic Fatty Liver Disease. Journal of the American Society of Nephrology, 19, 1564-1570.
https://doi.org/10.1681/asn.2007101155
[6] Makri, E., Goulas, A. and Polyzos, S.A. (2021) Epidemiology, Pathogenesis, Diagnosis and Emerging Treatment of Nonalcoholic Fatty Liver Disease. Archives of Medical Research, 52, 25-37.
https://doi.org/10.1016/j.arcmed.2020.11.010
[7] den Besten, G., van Eunen, K., Groen, A.K., Venema, K., Reijngoud, D. and Bakker, B.M. (2013) The Role of Short-Chain Fatty Acids in the Interplay between Diet, Gut Microbiota, and Host Energy Metabolism. Journal of Lipid Research, 54, 2325-2340.
https://doi.org/10.1194/jlr.r036012
[8] Cummings, J.H., Pomare, E.W., Branch, W.J., Naylor, C.P. and Macfarlane, G.T. (1987) Short Chain Fatty Acids in Human Large Intestine, Portal, Hepatic and Venous Blood. Gut, 28, 1221-1227.
https://doi.org/10.1136/gut.28.10.1221
[9] Murase, M., Kimura, Y. and Nagata, Y. (1995) Determination of Portal Short-Chain Fatty Acids in Rats Fed Various Dietary Fibers by Capillary Gas Chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 664, 415-420.
https://doi.org/10.1016/0378-4347(94)00491-m
[10] Fushimi, T., Suruga, K., Oshima, Y., Fukiharu, M., Tsukamoto, Y. and Goda, T. (2006) Dietary Acetic Acid Reduces Serum Cholesterol and Triacylglycerols in Rats Fed a Cholesterol-Rich Diet. British Journal of Nutrition, 95, 916-924.
https://doi.org/10.1079/bjn20061740
[11] Todesco, T., Rao, A., Bosello, O. and Jenkins, D. (1991) Propionate Lowers Blood Glucose and Alters Lipid Metabolism in Healthy Subjects. The American Journal of Clinical Nutrition, 54, 860-865.
https://doi.org/10.1093/ajcn/54.5.860
[12] Stoddart, L.A., Smith, N.J. and Milligan, G. (2008) International Union of Pharmacology. LXXI. Free Fatty Acid Receptors FFA1,-2, and-3: Pharmacology and Pathophysiological Functions. Pharmacological Reviews, 60, 405-417.
https://doi.org/10.1124/pr.108.00802
[13] Hong, Y.H., Nishimura, Y., Hishikawa, D., Tsuzuki, H., Miyahara, H., Gotoh, C., et al. (2005) Acetate and Propionate Short Chain Fatty Acids Stimulate Adipogenesis via GPCR43. Endocrinology, 146, 5092-5099.
https://doi.org/10.1210/en.2005-0545
[14] Ikeda, T., Nishida, A., Yamano, M. and Kimura, I. (2022) Short-Chain Fatty Acid Receptors and Gut Microbiota as Therapeutic Targets in Metabolic, Immune, and Neurological Diseases. Pharmacology & Therapeutics, 239, Article ID: 108273.
https://doi.org/10.1016/j.pharmthera.2022.108273
[15] Zaibi, M.S., Stocker, C.J., O’Dowd, J., Davies, A., Bellahcene, M., Cawthorne, M.A., et al. (2010) Roles of GPR41 and GPR43 in Leptin Secretory Responses of Murine Adipocytes to Short Chain Fatty Acids. FEBS Letters, 584, 2381-2386.
https://doi.org/10.1016/j.febslet.2010.04.027
[16] Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M.A., Motoike, T., Kedzierski, R.M., et al. (2004) Short-Chain Fatty Acids Stimulate Leptin Production in Adipocytes through the G Protein-Coupled Receptor GPR41. Proceedings of the National Academy of Sciences, 101, 1045-1050.
https://doi.org/10.1073/pnas.2637002100
[17] Jäger, S., Handschin, C., St.-Pierre, J. and Spiegelman, B.M. (2007) AMP-Activated Protein Kinase (AMPK) Action in Skeletal Muscle via Direct Phosphorylation of PGC-1alpha. Proceedings of the National Academy of Sciences, 104, 12017-12022.
https://doi.org/10.1073/pnas.0705070104
[18] Gao, Z., Yin, J., Zhang, J., Ward, R.E., Martin, R.J., Lefevre, M., et al. (2009) Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice. Diabetes, 58, 1509-1517.
https://doi.org/10.2337/db08-1637
[19] Alex, S., Lange, K., Amolo, T., Grinstead, J.S., Haakonsson, A.K., Szalowska, E., et al. (2013) Short-Chain Fatty Acids Stimulate Angiopoietin-Like 4 Synthesis in Human Colon Adenocarcinoma Cells by Activating Peroxisome Proliferator-Activated Receptor γ. Molecular and Cellular Biology, 33, 1303-1316.
https://doi.org/10.1128/mcb.00858-12
[20] den Besten, G., Bleeker, A., Gerding, A., van Eunen, K., Havinga, R., van Dijk, T.H., et al. (2015) Short-Chain Fatty Acids Protect against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch from Lipogenesis to Fat Oxidation. Diabetes, 64, 2398-2408.
https://doi.org/10.2337/db14-1213
[21] Canfora, E.E., Jocken, J.W. and Blaak, E.E. (2015) Short-Chain Fatty Acids in Control of Body Weight and Insulin Sensitivity. Nature Reviews Endocrinology, 11, 577-591.
https://doi.org/10.1038/nrendo.2015.128
[22] Fushimi, T., Tayama, K., Fukaya, M., Tsukamoto, Y., Kitakoshi, K., Nakai, N., et al. (2001) Acetic Acid Feeding Enhances Glycogen Repletion in Liver and Skeletal Muscle of Rats. The Journal of Nutrition, 131, 1973-1977.
https://doi.org/10.1093/jn/131.7.1973
[23] Tang, R. and Li, L. (2021) Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus. Canadian Journal of Infectious Diseases and Medical Microbiology, 2021, Article ID: 6632266.
[24] Aslamy, A., Wood, A.C., Jensen, E.T., Bertoni, A.G., Sheridan, P.A., Wong, K.E., et al. (2024) Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES). Diabetes, 73, 385-390.
https://doi.org/10.2337/db23-0401
[25] Li, H.P., Chen, X. and Li, M.Q. (2013) Butyrate Alleviates Metabolic Impairments and Protects Pancreatic β Cell Function in Pregnant Mice with Obesity. International Journal of Clinical and Experimental Pathology, 6, 1574-1584.
[26] Li, X., Shimizu, Y. and Kimura, I. (2017) Gut Microbial Metabolite Short-Chain Fatty Acids and Obesity. Bioscience of Microbiota, Food and Health, 36, 135-140.
https://doi.org/10.12938/bmfh.17-010
[27] Yang, Q., Ouyang, J., Sun, F. and Yang, J. (2020) Short-Chain Fatty Acids: A Soldier Fighting against Inflammation and Protecting from Tumorigenesis in People with Diabetes. Frontiers in Immunology, 11, Article ID: 590685.
https://doi.org/10.3389/fimmu.2020.590685
[28] Guo, W., Zhang, Z., Li, L., Liang, X., Wu, Y., Wang, X., et al. (2022) Gut Microbiota Induces DNA Methylation via SCFAs Predisposing Obesity-Prone Individuals to Diabetes. Pharmacological Research, 182, Article ID: 106355.
https://doi.org/10.1016/j.phrs.2022.106355
[29] Horiuchi, H., Kamikado, K., Aoki, R., Suganuma, N., Nishijima, T., Nakatani, A., et al. (2020) Bifidobacterium animalis Subsp. Lactis GCL2505 Modulates Host Energy Metabolism via the Short-Chain Fatty Acid Receptor GPR43. Scientific Reports, 10, Article No. 4158.
https://doi.org/10.1038/s41598-020-60984-6
[30] Aragonès, G., González-García, S., Aguilar, C., Richart, C. and Auguet, T. (2019) Gut Microbiota-Derived Mediators as Potential Markers in Nonalcoholic Fatty Liver Disease. BioMed Research International, 2019, Article ID: 8507583.
https://doi.org/10.1155/2019/8507583
[31] Psichas, A., Sleeth, M.L., Murphy, K.G., Brooks, L., Bewick, G.A., Hanyaloglu, A.C., et al. (2015) The Short Chain Fatty Acid Propionate Stimulates GLP-1 and PYY Secretion via Free Fatty Acid Receptor 2 in Rodents. International Journal of Obesity, 39, 424-429.
https://doi.org/10.1038/ijo.2014.153
[32] Tolhurst, G., Heffron, H., Lam, Y.S., Parker, H.E., Habib, A.M., Diakogiannaki, E., et al. (2012) Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2. Diabetes, 61, 364-371.
https://doi.org/10.2337/db11-1019
[33] 纪立伟, 郭立新. 胰高糖素样肽-1类药物的心血管保护作用[J]. 中华糖尿病杂志, 2020, 12(8): 654-660.
[34] Svegliati‐Baroni, G., Saccomanno, S., Rychlicki, C., Agostinelli, L., De Minicis, S., Candelaresi, C., et al. (2011) Glucagon‐Like Peptide‐1 Receptor Activation Stimulates Hepatic Lipid Oxidation and Restores Hepatic Signalling Alteration Induced by a High‐Fat Diet in Nonalcoholic Steatohepatitis. Liver International, 31, 1285-1297.
https://doi.org/10.1111/j.1478-3231.2011.02462.x
[35] Robertson, M.D., Bickerton, A.S., Dennis, A.L., Vidal, H. and Frayn, K.N. (2005) Insulin-Sensitizing Effects of Dietary Resistant Starch and Effects on Skeletal Muscle and Adipose Tissue Metabolism. The American Journal of Clinical Nutrition, 82, 559-567.
https://doi.org/10.1093/ajcn/82.3.559
[36] Kimura, I., Ozawa, K., Inoue, D., Imamura, T., Kimura, K., Maeda, T., et al. (2013) The Gut Microbiota Suppresses Insulin-Mediated Fat Accumulation via the Short-Chain Fatty Acid Receptor GPR43. Nature Communications, 4, Article No. 1829.
https://doi.org/10.1038/ncomms2852
[37] Freeland, K.R. and Wolever, T.M.S. (2010) Acute Effects of Intravenous and Rectal Acetate on Glucagon-Like Peptide-1, Peptide YY, Ghrelin, Adiponectin and Tumour Necrosis Factor-α. British Journal of Nutrition, 103, 460-466.
https://doi.org/10.1017/s0007114509991863
[38] 孔小娟, 乔江, 雷磊. 苍附导痰汤加减治疗多囊卵巢综合征伴胰岛素抵抗(痰湿证)的临床研究[J]. 中药新药与临床药理, 2025, 36(5): 806-813.
[39] 李志坤, 魏丹蕾, 杨树月, 等. 柴胡桂枝干姜汤对2型糖尿病大鼠肠道菌群及短链脂肪酸的影响研究[J]. 陕西中医, 2024, 45(6): 757-762.
[40] 张芮. 导痰汤中多糖的结构鉴定及调节脂质代谢和抗肥胖作用机制研究[D]: [硕士学位论文]. 扬州: 扬州大学, 2025.
[41] 朱琳, 陈学志, 李菲, 等. 化浊健脾通络方对缺血性卒中合并糖尿病大鼠的影响及作用机制[J]. 现代中西医结合杂志, 2025, 34(23): 3225-3231.
[42] 闫聪. 基于“脾为之卫”理论探讨参苓白术散通过肠道免疫调控肠屏障防治T2DM的作用机制[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2025.
[43] 王玉学. 基于SCFAs-AMPK通路探讨苡苓化浊方防治代谢相关脂肪性肝病作用机制的研究[D]: [硕士学位论文]. 济南: 山东中医药大学, 2024.
[44] 彭岚玉, 李定祥, 姚敬心, 等. 基于肠道菌群及其代谢产物SCFA探讨左归降糖通脉方对2型糖尿病大鼠糖脂代谢的影响[J]. 湖南中医药大学学报, 2024, 44(3): 365-373.
[45] 陈芳, 庞书勤, 朱旭, 等. 基于肠道双歧杆菌和IL-10/STAT3信号通路探讨薯蓣粥对2型糖尿病大鼠的降糖机制[J]. 福建中医药, 2025, 56(2): 48-52.
[46] 李红红, 王浩, 崔子龙, 等. 基于短链脂肪酸受体通路探讨逍遥散调节慢性应激大鼠糖代谢异常机制[J]. 中华中医药杂志, 2024, 39(12): 6466-6471.
[47] 李怡梅. 降糖三黄片调控肠道菌群/SCFAs/PI3K信号通路改善T2DM小鼠糖脂代谢的机制研究[D]: [硕士学位论文]. 广州: 广州中医药大学, 2024.
[48] 孙玲玲. 津力达颗粒治疗2型糖尿病(气阴两虚挟瘀型)的临床观察及对其肠道菌群、SCFAs的影响[D]: [硕士学位论文]. 郑州: 河南中医药大学, 2024.
[49] 李思韵, 蔡宏桂, 张珏, 等. 茵陈五苓散加减治疗2型糖尿病临床研究[J]. 新中医, 2024, 56(11): 7-11.
[50] 林巧妮. 中药复方益糖康调控肠道菌群改善2型糖尿病胰岛素抵抗的机制[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2024.
[51] 张怡. 白藜芦醇通过重塑“肠道菌群-短链脂肪酸”轴改善糖尿病肾病的作用及机制研究[D]: [硕士学位论文]. 重庆: 重庆医科大学, 2024.
[52] 徐崎瑞, 张莹. 赤松茸粗多糖缓解CCl4诱导的急性肝损伤及肠道稳态的调节作用[C]//中国营养学会益生菌益生元与健康分会. 第七届国际益生菌益生元科学大会摘要集. 兰州: 兰州大学公共卫生学院, 2025: 94.
[53] 王晓婷, 曹翠, 刘军锋, 等. 基于肠道菌群代谢探讨黄精多糖对酒精性肝病小鼠的保护作用[J]. 中草药, 2025, 56(16): 5814-5825.
[54] 宫汝淳, 李小丽, 田其濡, 等. 桑黄多糖对高脂血症小鼠肝脏氧化应激、肠道微生物多样性及短链脂肪酸的影响[J]. 饲料工业, 2025, 46(21): 101-108.
[55] 毕永慧, 李曦, 杨丹凤. 虫草素降血脂作用及其相关机制的实验研究进展[J]. 营养学报, 2025, 47(6): 612-617.
[56] 曹欣怡, 叶路芬, 陈昕, 等. 葛根素对脂多糖致抑郁模型小鼠行为学及肠道菌群代谢物的作用[J]. 解放军药学学报, 2024, 37(3): 227-234.
[57] 陈梦元. 菊芋多糖对Ⅱ型糖尿病小鼠血糖调节及肠道菌群的影响[D]: [硕士学位论文]. 武汉: 武汉轻工大学, 2025.
[58] 王京峰, 冯硕, 曹炫, 等. 枸杞多糖介导肠道菌群重塑改善2型糖尿病大鼠的糖脂异常[J]. 中国组织工程研究, 2026, 30(29): 7592-7602.
[59] 尚子慧. 基于“药效-代谢组学-关键通路”探讨山茱萸多糖抗2型糖尿病的作用机制[D]: [硕士学位论文]. 郑州: 河南中医药大学, 2024.
[60] 李婷. 甘草提取物干预肠道菌群变化对脂肪酸代谢的影响及其机制探索[J]. 生物化工, 2025, 11(6): 107-112.
[61] 王爽. 基于肠道菌群-胆汁酸途径探究忍冬苷调节肝脏脂肪酸代谢的作用及机制研究[D]: [硕士学位论文]. 南宁: 广西医科大学, 2025.
[62] 王洋, 周瑞娜, 雷莉妍, 等. 基于肠道菌群研究沙苑子总黄酮治疗慢性肝损伤的作用机制[J]. 中国中药杂志, 2025, 50(18): 5016-5025.
[63] 陶可欣. 三叶青活性成分干预酒精性脂肪肝及其机制探究[D]: [硕士学位论文]. 南昌: 南昌大学, 2024.
[64] 刘文文. 基于肠道微生物探讨茯苓多糖通过短链脂肪酸缓解肥胖相关脂肪组织胰岛素抵抗的作用机制研究[D]: [硕士学位论文]. 合肥: 安徽中医药大学, 2025.
[65] 颜美秋, 杨志远, 余冰清, 等. 基于短链脂肪酸-GPR43-GLP1信号轴研究铁皮石斛多糖对糖尿病前期的作用及机制[J]. 中草药, 2026, 57(1): 164-174.
[66] 和佳鸳, 徐虹, 曹杰, 等. 菊粉对2型糖尿病模型小鼠血清中3种短链脂肪酸的影响[J]. 江苏预防医学, 2025, 36(5): 583-586+595.
[67] 张义圆. 石榴皮多糖调节非酒精性脂肪肝小鼠肠道菌群的作用[D]: [硕士学位论文]. 成都: 成都大学, 2024.
[68] 柯玉. 以活性多糖为靶标的荷叶功能成分提取及其控糖降脂作用研究[D]: [硕士学位论文]. 广州: 华南理工大学, 2024.
[69] 黄文浩. 纳米硒负载姜黄素改善酒精性肝损伤的作用机制研究[D]: [博士学位论文]. 湛江: 广东海洋大学, 2024.