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钠-葡萄糖共转运体-2抑制剂在糖尿病肾病中的作用机制及临床意义

王宇佳, 郝传明^*

复旦大学附属华山医院肾病科，复旦大学肾脏病研究所，上海 200040

摘要

利用钠-葡萄糖共转运体-2 (sodium-glucose cotransporter 2, SGLT-2)抑制剂治疗糖尿病和糖尿病肾病(diabetic kidney disease, DKD)成为近年来糖尿病领域的研究热点，与传统降糖药相比，SGLT-2抑制剂具有多种独特优势，其肾脏和心血管保护作用最为突出。SGLT-2抑制剂肾脏保护机制主要包括改善肾小球高滤过、降低血尿酸水平、抑制肾小管增生肥大和肾间质纤维化、调节肾内肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)功能等；其心血管保护机制主要包括降低血压、缓解血糖波动、改善胰岛素敏感性，以及改善机体能量代谢和脂肪分布等。SGLT-2抑制剂使用中可能存在的不良反应包括生殖道感染和急性肾损伤等，这些问题也需得到足够重视和关注以保障SGLT-2抑制剂临床使用的安全性。

关键词： 糖尿病肾病; 钠-葡萄糖共转运体-2; 肾小球高滤过; 尿酸; 肾小管病变; 血压; 能量代谢; 不良反应

分类号：R334;R692

The mechanisms and clinical potential: sodium-glucose cotransporter 2 (SGLT-2) inhibitors treating diabetic kidney disease

WANG Yu-Jia, HAO Chuan-Ming^*

Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai 200040, China

Abstract

The employment of sodium-glucose cotransporter 2 (SGLT-2) inhibitors in the treatment of diabetes mellitus and diabetic kidney disease (DKD) becomes a hot topic in recent years. Compared with traditional glucose-lowering drugs, SGLT-2 inhibitors present distinctive advantages in renal and cardiovascular protection. The mechanisms for renal protection include attenuating glomerular hyperfiltration, lowering serum uric acid, alleviating tubular lesions and regulating intrarenal renin-angiotensin-aldosterone system (RAAS) dysfunction. In addition, the lowering blood pressure, blunting blood glucose fluctuation, increasing insulin sensitivity, optimizing energy metabolism and body fat distribution account for the cardiovascular protective effects of SGLT-2 inhibitors. However, their potential adverse reactions and safety concerns should be carefully addressed in clinical usage.

Key words: diabetic nephropathies; sodium-glucose cotransporter 2; glomerular hyperfiltration; uric acid; tubular lesions; blood pressure; energy metabolism; adverse reactions

收稿日期：2018-06-05　　录用日期：2018-11-11

通讯作者：郝传明　　E-mail: Chuanminghao@fudan.edu.cn

DOI: 10.13294/j.aps.2018.0081

引用本文：

王宇佳, 郝传明. 钠-葡萄糖共转运体-2抑制剂在糖尿病肾病中的作用机制及临床意义[J]. 生理学报 2018; 70 (6): 663-669.

WANG Yu-Jia, HAO Chuan-Ming. The mechanisms and clinical potential: sodium-glucose cotransporter 2 (SGLT-2) inhibitors treating diabetic kidney disease. Acta Physiol Sin 2018; 70 (6): 663-669 (in Chinese with English abstract).