钠-葡萄糖协同转运蛋白2抑制剂治疗射血分数保留性心力衰竭的循证医学证据及机制

Evidence-based Medicine and Mechanism of Sodium-glucose Cotransporter 2 Inhibitor in the Treatment of Heart Failure with Preserved Ejection Fraction

钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是一种新型降糖药物,其通过阻断位于肾脏近端小管的低亲和力、高容量的SGLT2,减少近端小管对葡萄糖的重吸收和增加尿中葡萄糖的排泄率来降低血糖。研究显示,SGLT2还可以降低心力衰竭住院风险和减少心血管事件。目前,SGLT2抑制剂在射血分数降低的心力衰竭(HFrEF)治疗中的价值已经明确,其对射血分数保留性心力衰竭(HFpEF)也存在一定的治疗价值,但具体机制尚不清楚。本文首先系统阐述了SGLT2抑制剂治疗HFpEF的循证医学证据,然后深入分析了SGLT2抑制剂治疗HFpEF的机制,指出SGLT2抑制剂通过利尿、利钠、降低血压、减轻体质量、控制血糖、抑制炎症反应和氧化应激、改善心肌能量代谢、抑制Na+/H+交换、改善心肌离子稳态、促进自噬和溶酶体降解、减少心外膜脂肪等机制来改善HFpEF患者的临床症状及降低患者心血管不良事件发生风险,这为HFpEF的临床治疗提供了一定参考。

Sodium glucose cotransporter 2(SGLT2)inhibitor is a new hypoglycemic drug.It reduces blood glucose by blocking the low affinity and high-volume SGLT2 located in the proximal tubule of the kidney,reducing the reabsorption of glucose in the proximal tubule and increasing the excretion rate of glucose in urine.Studies have shown that SGLT2 can also reduce the risk of hospitalization for heart failure and reduce cardiovascular events.At present,the value of SGLT2 inhibitors in the treatment of heart failure with reduced ejection fraction(HFrEF)has been clarified,and it also has a certain therapeutic value in heart failure with preserved ejection fraction(HFpEF),but its specific mechanism is still unclear.This paper first systematically expounds the evidence-based medical evidence of SGLT2 inhibitor in the treatment of HFpEF,and then deeply analyzes the mechanism of SGLT2 inhibitor in the treatment of HFpEF,and points out that SGLT2 inhibitor can improve the clinical symptoms of HFpEF patients and reduce the risk of cardiovascular adverse events through mechanisms including diuresis,natriuretic and reducing blood pressure,reducing body weight and controlling blood glucose,inhibiting inflammatory response and oxidative stress,improving myocardial energy metabolism,inhibiting Na+/H+exchange and improving myocardial ion homeostasis,promoting autophagy and lysosomal degradation,reducing epicardial fat,etc.This provides a certain reference for the clinical treatment of HFpEF.