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摘要: 钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂已成为治疗心力衰竭(心衰)的新兴药物，但其作用机制尚不清楚。健康人心肌细胞仅表达SGLT1，SGLT2定位在肾脏近曲小管和心外膜脂肪组织(EAT)，在疾病状态下高表达。舒张性心衰患者发生EAT堆积，EAT高表达SGLT2和分泌脂肪细胞因子，介导心肌纤维化和心肌肥厚；心肌细胞高表达SGLT1介导细胞内Na+超载。基于SGLT2/1在心脏和肾脏的分布，我们推测SGLT2抑制剂治疗心衰的潜在作用机制主要涉及心脏血流动力学和心脏代谢重构，EAT-SGLT2可能是心脏代谢重构防治的重要靶点。
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关键词:
- 心力衰竭 /
- 钠-葡萄糖协同转运蛋白2抑制剂 /
- 心外膜脂肪组织 /
- 钠-葡萄糖协同转运蛋白2/1 /
- 心脏代谢重构
Abstract: The efficacy of sodium glucose cotransporter 2(SGLT2) inhibitors in the treatment of heart failure have been demonstrated in cardiovascular outcome trials, but its mechanism is not clear. Cardiomyocytes in healthy human only express SGLT1, and SGLT2 is localized in renal proximal convoluted tubules and epicardial adipose tissue(EAT), which is highly expressed in disease state. EAT accumulation occurs in patients with diastolic heart failure. EAT highly expresses SGLT2 and secretes adipocytokines, which mediates myocardial fibrosis and myocardial hypertrophy; High expression of SGLT1 in cardiomyocytes mediates intracellular Na+overload. Based on the distribution of SGLT2/1 in heart and kidney, we speculate that the potential mechanism of SGLT2 inhibitor in the treatment of heart failure mainly involves cardiac hemodynamics and cardiac metabolic remodeling. EAT-SGLT2 may be an important target for the prevention and treatment of cardiac metabolic remodeling. -
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图 1 SGLT2抑制剂治疗心衰的潜在作用机制
Figure 1. The potential mechanisms of SGLT2 inhibitors in heart failure
表 1 SGLT2抑制剂降低EAT容积或厚度的临床研究
Table 1. Clinical research of the SGLT2 inhibitors reduced volume or thickness of the EAT
药物 T2DM/例 治疗时间 EAT检测方法 EAT结果 参考文献 SGLT2抑制剂 53 24周 超声心动图 (37.8±17.2) cm3：(20.7±7.0) cm3，P < 0.001 [27] 卡格列净Canagliflozin 13 6个月 超声心动图 (9.3 ± 2.5) mm：(7.3 ± 2.0) mm，P < 0.001 [28] 鲁格列净Luseogliflozin 19 12周 心脏磁共振 117(96，136) cm3：111(88，134) cm3，P=0.048 [29] 达格列净Dapagliflozin 40 6个月 超声心动图 (16.4 ± 8.3) cm3：(4.7 ± 8.8) cm3，P=0.01 [30] 依格列净Lpragliflozin 9 12周 心脏磁共振 102(79，126) cm3：89(66，109) cm3，P=0.008 [31] 恩格列净Empagliflozin 56 12周 心脏磁共振 V1(108.5 ± 31.8) mL：V3(106.9 ± 31.8) mL，P=0.09 [32] 
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