晚期糖基化终产物在糖尿病肾病中的致病作用及防治策略
Pathogenic Role and Preventive Strategy of Advanced Glycation End Products in Diabetic Kidney Disease
DOI: 10.12677/ACM.2023.13102220, PDF,    科研立项经费支持
作者: 李 燕:暨南大学附属广州红十字会医院肾内科,广东 广州;暨南大学附属广州红十字会医院病态营养研究所临床营养科,广东 广州;谭荣韶*:暨南大学附属广州红十字会医院病态营养研究所临床营养科,广东 广州
关键词: 晚期糖基化终产物糖尿病肾病慢性肾脏病Advanced Glycation End Products Diabetic Kidney Disease Chronic Kidney Disease
摘要: 糖尿病肾病(DKD)是糖尿病主要的微血管并发症之一,是导致糖尿病患者发病和死亡的主要原因,也是导致终末期肾病(ESRD)的主要原因,严重危害人类健康。DKD的发生与持续高血糖密切相关,体内高糖环境下积聚的晚期糖基化终产物(AGEs)是DKD的主要致病因素。AGEs在体内的持续蓄积会引起一系列氧化应激等级联反应及激活多条信号通路,最终导致肾脏损伤。AGEs在DKD发生发展过程中的作用是近年来的研究热点。本文就AGEs的来源、生化特性、病理生理机制及相关防治策略作如下综述。
Abstract: Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus, which is the main cause of morbidity and mortality in diabetes mellitus patients, and also the main cause of end-stage renal disease (ESRD), which is a serious hazard to human health. DKD is closely related to persistent hyperglycemia, and the accumulation of advanced glycation end products (AGEs) in the body under the environment of high glucose is a major pathogenic factor in DKD. The accumulation of AGEs in the body causes a series of oxidative stress cascade reactions and activation of multiple signalling pathways, which ultimately leads to kidney injury. The role of AGEs in the de-velopment of DKD has been a hot topic of research in recent years. In this paper, we review the sources, biochemical properties, pathophysiological mechanisms and prevention strategies of AGEs.
文章引用:李燕, 谭荣韶. 晚期糖基化终产物在糖尿病肾病中的致病作用及防治策略[J]. 临床医学进展, 2023, 13(10): 15883-15890. https://doi.org/10.12677/ACM.2023.13102220

参考文献

[1] Vallon, V. and Thomson, S.C. (2020) The Tubular Hypothesis of Nephron Filtration and Diabetic Kidney Disease. Na-ture Reviews Nephrology, 16, 317-336. [Google Scholar] [CrossRef] [PubMed]
[2] Kato, M. and Natarajan, R. (2019) Epigenetics and Epigenomics in Diabetic Kidney Disease and Metabolic Memory. Nature Reviews Nephrology, 15, 327-345. [Google Scholar] [CrossRef] [PubMed]
[3] Anders, H.J., Huber, T.B., Isermann, B., et al. (2018) CKD in Diabetes: Diabetic Kidney Disease versus Nondiabetic Kidney Disease. Nature Reviews Nephrology, 14, 361-377. [Google Scholar] [CrossRef] [PubMed]
[4] Azushima, K., Gurley, S.B. and Coffman, T.M. (2018) Modelling Diabetic Nephropathy in Mice. Nature Reviews Nephrology, 14, 48-56. [Google Scholar] [CrossRef] [PubMed]
[5] Molitch, M.E., Adler, A.I., Flyvbjerg, A., et al. (2015) Diabetic Kid-ney Disease: A Clinical Update from Kidney Disease: Improving Global Outcomes. Kidney International, 87, 20-30. [Google Scholar] [CrossRef] [PubMed]
[6] Majchrzak, C., Cougnard-Gregoire, A., Le-Goff, M., et al. (2022) Skin Autofluorescence of Advanced Glycation End-Products and Mortality in Older Adults: The Roles of Chronic Kidney Disease and Diabetes. Nutrition, Metabolism and Cardiovascular Diseases, 32, 2526-2533. [Google Scholar] [CrossRef] [PubMed]
[7] Wu, X.Q., Zhang, D.D., Wang, Y.N., et al. (2021) AGE/RAGE in Diabetic Kidney Disease and Ageing Kidney. Free Radical Biology and Medicine, 171, 260-271. [Google Scholar] [CrossRef] [PubMed]
[8] Byun, K., Yoo, Y., Son, M., et al. (2017) Advanced Glycation End-Products Produced Systemically and by Macrophages: A Common Contributor to Inflammation and De-generative Diseases. Pharmacology & Therapeutics, 177, 44-55. [Google Scholar] [CrossRef] [PubMed]
[9] Yacoub, R., Nugent, M., Cai, W., et al. (2017) Advanced Glycation end Products Dietary Restriction Effects on Bacterial Gutmicrobiota in Peritoneal Dialysis Patients; a Random-ized Open Label Controlled Trial. PLOS ONE, 12, e184789. [Google Scholar] [CrossRef] [PubMed]
[10] Rungratanawanich, W., Qu, Y., Wang, X., et al. (2021) Ad-vanced Glycation End Products (AGEs) and Other Adducts in Aging-Related Diseases and Alcohol-Mediated Tissue Injury. Experimental & Molecular Medicine, 53, 168-188. [Google Scholar] [CrossRef] [PubMed]
[11] Yamagishi, S. and Matsui, T. (2010) Advanced Glycation End Products, Oxidative Stress and Diabetic Nephropathy. Oxidative Medicine and Cellular Longevity, 3, 101-108. [Google Scholar] [CrossRef] [PubMed]
[12] Shu, M., Cheng, W., Jia, X., et al. (2023) AGEs Promote Atheroscle-rosis by Increasing LDL Transcytosis across Endothelial Cells via RAGE/NF-kappaB/Caveolin-1 Pathway. Molecular Medicine, 29, Article No. 113. [Google Scholar] [CrossRef] [PubMed]
[13] Chaudhuri, J., Bains, Y., Guha, S., et al. (2018) The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality. Cell Metabo-lism, 28, 337-352. [Google Scholar] [CrossRef] [PubMed]
[14] Fotheringham, A.K., Gallo, L.A., Borg, D.J., et al. (2022) Ad-vanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney? Nutri-ents, 14, Article No. 2675. [Google Scholar] [CrossRef] [PubMed]
[15] Steenbeke, M., Speeckaert, R., Desmedt, S., et al. (2022) The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases. International Journal of Molecular Sci-ences, 23, Article No. 3439. [Google Scholar] [CrossRef] [PubMed]
[16] Kumar, P.A., Chitra, P.S. and Reddy, G.B. (2016) Advanced Glycation End Products Mediated Cellular and Molecular Events in the Pathology of Diabetic Nephropathy. BioMolecular Con-cepts, 7, 293-309. [Google Scholar] [CrossRef] [PubMed]
[17] 叶成松, 王贻坤, 叶山东. 晚期糖基化终末产物的特性及其检测[J]. 国际病理科学与临床杂志, 2013, 33(2): 175-178.
[18] Thurlow, J.S., Joshi, M., Yan, G., et al. (2021) Global Epidemiology of End-Stage Kidney Disease and Disparities in Kidney Replacement Therapy. American Journal of Nephrology, 52, 98-107. [Google Scholar] [CrossRef] [PubMed]
[19] Poojary, M.M. and Lund, M.N. (2022) Chemical Stability of Proteins in Foods: Oxidation and the Maillard Reaction. Annual Review of Food Science and Technology, 13, 35-58. [Google Scholar] [CrossRef] [PubMed]
[20] Poulsen, M.W., Hedegaard, R.V. andersen, J.M., et al. (2013) Advanced Glycation End Products in Food and Their Effects on Health. Food and Chemical Toxicol-ogy, 60, 10-37. [Google Scholar] [CrossRef] [PubMed]
[21] Liang, Z., Chen, X., Yang, Z., et al. (2022) Sodium Ions Affect Pyrraline Formation in the Maillard Reaction with Lys-Containing Dipeptides and Tripeptides. Frontiers in Nutrition, 9, Article ID: 874650. [Google Scholar] [CrossRef] [PubMed]
[22] Liu, R., Zhang, M., Xu, L., et al. (2022) Fluorescent Advanced Glycation End Products in Type 2 Diabetes and Its Association with Diabetes Duration, Hemoglobin A1c, and Diabetic Complications. Frontiers in Nutrition, 9, Article ID: 1083872. [Google Scholar] [CrossRef] [PubMed]
[23] Nakano, T., Mizumasa, T., Kuroki, Y., et al. (2020) Advanced Glycation End Products Are Associated with Immature Angiogenesis and Peritoneal Dysfunction in Patients on Perito-neal Dialysis. Peritoneal Dialysis International, 40, 67-75. [Google Scholar] [CrossRef] [PubMed]
[24] Jiang, J., Chen, P., Chen, J., et al. (2012) Accumulation of Tissue Advanced Glycation End Products Correlated with Glucose Exposure Dose and Associated with Cardiovascular Morbidity in Patients on Peritoneal Dialysis. Atherosclerosis, 224, 187-194. [Google Scholar] [CrossRef] [PubMed]
[25] Meerwaldt, R., Hartog, J.W., Graaff, R., et al. (2005) Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Pre-dicts Mortality in Hemodialysis Patients. Journal of the American Society of Nephrology, 16, 3687-3693. [Google Scholar] [CrossRef
[26] Arsov, S., Graaff, R., Morariu, A.M., et al. (2010) Does Hepatitis C Increase the Accumulation of Advanced Glycation End Products in Haemodialysis Patients? Nephrology Dialysis Transplantation, 25, 885-891. [Google Scholar] [CrossRef] [PubMed]
[27] Koyama, H. and Nishizawa, Y. (2010) AGEs/RAGE in CKD: Irreversible Metabolic Memory Road toward CVD? European Journal of Clinical Investigation, 40, 623-635. [Google Scholar] [CrossRef] [PubMed]
[28] Thornalley, P.J. (2006) Advanced Glycation End Products in Renal Failure. Journal of Renal Nutrition, 16, 178-184. [Google Scholar] [CrossRef] [PubMed]
[29] Dozio, E., Caldiroli, L., Molinari, P., et al. (2023) Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease. Antioxidants (Basel), 12, Article No. 584. [Google Scholar] [CrossRef] [PubMed]
[30] Gnudi, L., Coward, R. and Long, D.A. (2016) Diabetic Nephropathy: Perspective on Novel Molecular Mechanisms. Trends in Endocrinology and Metabolism, 27, 820-830. [Google Scholar] [CrossRef] [PubMed]
[31] Reidy, K., Kang, H.M., Hostetter, T., et al. (2014) Molecular Mechanisms of Diabetic Kidney Disease. Journal of Clinical Investigation, 124, 2333-2340. [Google Scholar] [CrossRef
[32] Bansode, S., Bashtanova, U., Li, R., et al. (2020) Glycation Changes Mo-lecular Organization and Charge Distribution in Type I Collagen Fibrils. Scientific Reports, 10, Article No. 3397. [Google Scholar] [CrossRef] [PubMed]
[33] Hadley, J.C., Meek, K.M. and Malik, N.S. (1998) Glycation Changes the Charge Distribution of Type I Collagen Fibrils. Glycoconjugate Journal, 15, 835-840. [Google Scholar] [CrossRef
[34] Cepas, V., Collino, M., Mayo, J.C., et al. (2020) Redox Signaling and Advanced Glycation End Products (AGEs) in Diet-Related Diseases. Antioxidants (Basel), 9, Article No. 142. [Google Scholar] [CrossRef] [PubMed]
[35] Gill, P.S. and Wilcox, C.S. (2006) NADPH Oxidases in the Kidney. Antioxidants & Redox Signaling, 8, 1597-1607. [Google Scholar] [CrossRef] [PubMed]
[36] Dozio, E., Vettoretti, S., Lungarella, G., et al. (2021) Sarcopenia in Chronic Kidney Disease: Focus on Advanced Glycation End Products as Mediators and Markers of Oxidative Stress. Biomedicines, 9, Article No. 405. [Google Scholar] [CrossRef] [PubMed]
[37] Xie, J., Mendez, J.D., Mendez-Valenzuela, V., et al. (2013) Cellular Signalling of the Receptor for Advanced Glycation End Products (RAGE). Cell Signaling, 25, 2185-2197. [Google Scholar] [CrossRef] [PubMed]
[38] Goldin, A., Beckman, J.A., Schmidt, A.M., et al. (2006) Ad-vanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury. Circulation, 114, 597-605. [Google Scholar] [CrossRef
[39] Liebisch, M., Bondeva, T., Franke, S., et al. (2014) Activation of the Receptor for Advanced Glycation End Products Induces Nuclear Inhibitor of Protein Phospha-tase-1 Suppression. Kidney International, 86, 103-117. [Google Scholar] [CrossRef] [PubMed]
[40] Matoba, K., Takeda, Y., Nagai, Y., et al. (2020) Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease. Biomedicines, 8, Article No. 40. [Google Scholar] [CrossRef] [PubMed]
[41] Duni, A., Liakopoulos, V., Roumeliotis, S., et al. (2019) Oxida-tive Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread. International Journal of Molecular Sciences, 20, Article No. 3711. [Google Scholar] [CrossRef] [PubMed]
[42] Chao, P.C., Huang, C.N., Hsu, C.C., et al. (2010) Association of Die-tary AGEs with Circulating AGEs, Glycated LDL, IL-1alpha and MCP-1 Levels in Type 2 Diabetic Patients. European Journal of Nutrition, 49, 429-434. [Google Scholar] [CrossRef] [PubMed]
[43] Uribarri, J. and He, J.C. (2015) The Low AGE Diet: A Neglected Aspect of Clinical Nephrology Practice? Nephron, 130, 48-53. [Google Scholar] [CrossRef] [PubMed]
[44] Jung, E., Kang, W.S., Jo, K., et al. (2019) Ethyl Pyruvate Prevents Renal Damage Induced by Methylglyoxal-Derived Advanced Glycation End Products. Journal of Diabetes Research, 2019, Article ID: 4058280. [Google Scholar] [CrossRef] [PubMed]
[45] Lin, J., Gwyneth, T.Y., Leong, L.P., et al. (2018) Steamed Bread En-riched with Quercetin as an Antiglycative Food Product: Its Quality Attributes and Antioxidant Properties. Food & Func-tion, 9, 3398-3407. [Google Scholar] [CrossRef
[46] Yin, M.C. (2015) Inhibitory Effects and Actions of Pentacyclic Triter-penes upon Glycation. Biomedicine (Taipei), 5, Article No. 13. [Google Scholar] [CrossRef] [PubMed]
[47] Jensen, L.J., Denner, L., Schrijvers, B.F., et al. (2006) Renal Ef-fects of a Neutralising RAGE-Antibody in Long-Term Streptozotocin-Diabetic Mice. Journal of Endocrinology, 188, 493-501. [Google Scholar] [CrossRef] [PubMed]
[48] Thornalley, P.J. (2003) Use of Aminoguanidine (Pimagedine) to Prevent the Formation of Advanced Glycation End Products. Archives of Biochemistry and Biophysics, 419, 31-40. [Google Scholar] [CrossRef] [PubMed]
[49] Degenhardt, T.P., Alderson, N.L., Arrington, D.D., et al. (2002) Pyridoxamine Inhibits Early Renal Disease and Dyslipidemia in the Streptozotocin-Diabetic Rat. Kidney International, 61, 939-950. [Google Scholar] [CrossRef] [PubMed]
[50] Yang, P.Y., Li, P.C. and Feng, B. (2019) Protective Effects of Gliclazide on High Glucose and AGEs-Induced Damage of Glomerular Mesangial Cells and Renal Tubular Epithelial Cells via Inhibiting RAGE-p22phox-NF-κB Pathway. European Review for Medical and Pharmacological Sciences, 23, 9099-9107.
[51] Muthenna, P., Raghu, G., Kumar, P.A., et al. (2014) Effect of Cinnamon and Its Procyanidin-B2 En-riched Fraction on Diabetic Nephropathy in Rats. Chemico-Biological Interactions, 222, 68-76. [Google Scholar] [CrossRef] [PubMed]
[52] Rabbani, N. and Thornalley, P.J. (2019) Glyoxalase 1 Modulation in Obesity and Diabetes. Antioxidants & Redox Signaling, 30, 354-374. [Google Scholar] [CrossRef] [PubMed]
[53] Wang, Z.H., Hsu, C.C., Huang, C.N., et al. (2010) Anti-Glycative Ef-fects of Oleanolic Acid and Ursolic Acid in Kidney of Diabetic Mice. European Journal of Pharmacology, 628, 255-260. [Google Scholar] [CrossRef] [PubMed]
[54] Kaida, Y., Fukami, K., Matsui, T., et al. (2013) DNA Aptamer Raised against AGEs Blocks the Progression of Experimental Diabetic Nephropathy. Diabetes, 62, 3241-3250. [Google Scholar] [CrossRef] [PubMed]
[55] Bucciarelli, L.G., Wendt, T., Rong, L., et al. (2002) RAGE Is a Mul-ti-Ligand Receptor of the Immunoglobulin Super-Family: Implications for Homeostasis and Chronic Disease. Cellular and Molecular Life Sciences, 59, 1117-1128. [Google Scholar] [CrossRef] [PubMed]
[56] Kawanishi, K., Honda, K., Tsukada, M., et al. (2013) Neutral So-lution Low in Glucose Degradation Products Is Associated with Less Peritoneal Fibrosis and Vascular Sclerosis in Pa-tients Receiving Peritoneal Dialysis. Peritoneal Dialysis International, 33, 242-251. [Google Scholar] [CrossRef] [PubMed]
[57] Van Tellingen, A., Schalkwijk, C.G., Teerlink, T., et al. (2005) Influ-ence of Different Haemodialysis Modalities on AGE Peptide Levels: Intradialytic versus Long-Term Results. Nephron Clinical Practice, 100, c1-c7. [Google Scholar] [CrossRef] [PubMed]
[58] Floridi, A., Antolini, F., Galli, F., et al. (2002) Daily Haemodialysis Im-proves Indices of Protein Glycation. Nephrology Dialysis Transplantation, 17, 871-878. [Google Scholar] [CrossRef] [PubMed]