康 斐,刘 冀

糖尿病肾病（Diabetic Nephropathy，DN）是糖尿病患者常见微血管并发症，也是终末期肾病（End-stage Renal disease，ESRD）的主要原因[1]。其发病机制复杂，涉及多种病理生理过程，其中氧化应激是推动DN进展的重要因素之一。高血糖状态下，肾脏内活性氧（Reactive Oxygen Species，ROS）过度生成损伤肾小球和肾小管细胞，诱发炎症、纤维化及血管损伤，最终导致肾衰竭[1-2]。本文系统综述GLP-1受体激动剂（Glucagon Like Peptide-1 Receptor Agoinst，GLP-1RA）对DN患者肾脏的保护机制和应用前景，为临床应用提供理论依据和研究方向。

GLP-1受体激动剂；胰高血糖素样肽-1；糖尿病肾病；血糖

[1] Venkatesan K,Cheryeth MMJ,Verghese AT,Mathews AM,avisankar N,Unnikrishnan P,Prakash V,Harimohan H,Haroon NN,James S,Cherian S.Finerenone and diabetic renal disease:a narrative review.Endocrine.2024Dec;86(3):882-889. [2] Zhang MZ,Bao W,Zheng QY,Wang YH,Sun LY.Efficacy and Safety of Finerenone in Chronic Kidney Disease:A Systematic Review and Meta-Analysis of Randomized Clinical Trials.Front Pharmacol.2022 Feb 7;13:819327. [3] JHA J,BANAL C,CHOW B,et al.Diabetes and kidney disease:Role of oxidative stress[J].Antioxid Redox Signal,2016,25(12):657–684. [4] 蒋镜清,符玲,谈梦璐,等.胰高血糖素样肽-1(GLP-1)类似物研究进展[J].高校化学工程学报,2020,34(06):1327-1338. [5] 王恬园,于芸,韩如泉.胰高血糖素样肽-1受体激动剂的临床应用及围术期研究进展[J].首都医科大学学报,2024,45(06):1115-1121. [6] Tasyurek HM,Altunbas HA,Balci MK,Sanlioglu S.Incretins:their physiology and application in the treatment of diabetes mellitus. Diabetes Metab Res Rev.2014 Jul;30(5):354-71. [7] Hussein H,Zaccardi F,Khunti K,et al.Efficacy andtolerability of sodium-glucose co-transporter-2 inhibitorsand glucagon-like peptide-1 receptor agonists:a system-atic review and network meta-analysis[J].Diabetes ObesMetab,2020,22(7):1035-1046. [8] Smits MM,Van Raalte DH.Safety of Semaglutide.Front Endocrinol(Lausanne).2021 Jul 7;12:645563. [9] Xie Z Y,Yang S S,Deng W S,et al.Efficacy andsafety of liraglutide and semaglutide on weight loss inpeople with obesity or overweight:a systematic review[J].Clin Epidemiol,2022,14:1463-1476. [10] American Diabetes Association Professional PracticeCommittee.16.Diabetes care in the hospital:standardsof care in diabetes-2024[J].Diabetes Care,2024,47(Suppl 1):S295-S306. [11] Skov J(2014)Effects of GLP-1 in the kidney.Rev Endocr Metab Disord 15(3):197–207. [12] Trang NN,Chung CC,Lee TW,Cheng WL,Kao YH,Huang SY,Lee TI,Chen YJ(2021)Empagliflozin and liraglutide differen-tially modulate cardiac metabolism in diabetic cardiomyopathy in rats.Int J Mol Sci 22(3):1177. [13] Gerstein HC,Sattar N,Rosenstock J,Ramasundarahettige C,Pratley R,Lopes RD,Lam C,Khurmi NS,Heenan L,Del Prato S,Dyal L,Branch K(2021)Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes.N Engl J Med 385(10):896–907. [14] Górriz JL,Soler MJ,Navarro-González JF,García-Carro C,Puchades MJ,D',Marco L,Martínez Castelao A,Fernán-dez-Fernández B,Ortiz A,Górriz-Zambrano C,Navarro-Pérez J,Gorgojo-Martinez JJ(2020)GLP-1 receptor agonists and dia-betic kidney disease:a call of attention to nephrologists.J Clin Med 9(4). [15] Skov J,Dejgaard A,Frøkiær J,Holst JJ,Jonassen T,Rittig S,Christiansen JS(2013)Glucagon-like peptide-1(GLP-1):effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men.J Clin Endocrinol Metab 98(4):E664–E671. [16] Kuang Z,Hou N,Kan C,Han F,Qiu H,Sun X.The protective effects of SGLT-2 inhibitors,GLP-1 receptor agonists,and RAAS blockers against renal injury in patients with type 2 diabetes.Int Urol Nephrol.2023 Mar;55(3):617-629. [17] Deb DK,Bao R,Li YC(2017)Critical role of the cAMP-PKA pathway in hyperglycemia-induced epigenetic activation of fibrogenic program in the kidney.FASEB J 31(5):2065–2075. [18] Marso SP,Bain SC,Consoli A,Eliaschewitz FG,Jódar E,Leiter LA,Lingvay I,Rosenstock J,Seufert J,Warren ML,Woo V,Hansen O,Holst AG,Pettersson J,Vilsbøll T(2016)Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N Engl J Med 375(19):1834–1844. [19] Kim M,Platt MJ,Shibasaki T,Quaggin SE,Backx PH,Seino S,Simpson JA,Drucker DJ(2013)GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure.Nat Med 19(5):567–575. [20] Berberich AJ,Hegele RA(2021)Lipid effects of glucagon-like peptide 1 receptor analogs.Curr Opin Lipidol 32(3):191–199. [21] Stemmer K,Finan B,DiMarchi RD,Tschöp MH,Müller TD(2020)Insights into incretin-based therapies for treatment of diabetic dyslipidemia.Adv Drug Deliv Rev 159:34–53.

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