Wang Fang-Zheng, Wei Wen-Bo, Li Xin, Huo Jun-Yu, Jiang Wan-Ying, Wang Hong-Yu, Qian Pei, Li Zhen-Zhen, Zhou Ye-Bo
Department of Physiology, Nanjing Medical University Nanjing 211166, Jiangsu, China.
Department of Cardiology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University Nanjing 210021, Jiangsu, China.
Am J Transl Res. 2021 Sep 15;13(9):10950-10961. eCollection 2021.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to improve glycemic control. This study was designed to investigate the effects of SGLT2i dapagliflozin (dapa) on cardiomyopathy induced by isoproterenol (ISO) and its potential mechanisms. Fifty male Sprague Dawley rats were randomly assigned to the control (n=10) and the ISO (2.5 mg/kg/day)-treated groups (n=40). After 2 weeks, the 28 surviving rats with obvious left ventricular dysfunction in the ISO group were randomized into three medication groups, including the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan group (S/V, n=9), the dapa group (n=9), and the ISO group (n=10) for 4 weeks. Next, electrical programmed stimulation was performed in all the groups to evaluate their susceptibility to ventricular arrhythmias (VAs). Compared to the ISO rats, the dapa administration not only effectively reduced the cumulative risk of death, the myocardial fibrosis, the plasma angiotensin II levels and its functional receptor AT1R protein expressions in the heart, and the proinflammatory cytokine levels in the cardiac tissue of the ISO-treated rats, but it also improved their cardiac function and inhibited oxidative stress. These effects were similar to S/V. However, dapa showed a greater efficacy than S/V in reducing the left ventricular end-diastolic volumes, lowing the heart rates and VAs, and decreasing the body weights and plasma glucose levels. The mechanisms by which dapa exerts protective effects on cardiomyopathy may be related to its indirect antioxidant capacity and direct hypoglycemic action.
据报道，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可改善血糖控制。本研究旨在探讨SGLT2i达格列净（dapa）对异丙肾上腺素（ISO）诱导的心肌病的影响及其潜在机制。将50只雄性Sprague Dawley大鼠随机分为对照组（n = 10）和ISO治疗组（2.5 mg/kg/天，n = 40）。2周后，将ISO组中28只存活且有明显左心室功能障碍的大鼠随机分为三个用药组，包括血管紧张素受体脑啡肽酶抑制剂（ARNI）沙库巴曲缬沙坦组（S/V，n = 9）、dapa组（n = 9）和ISO组（n = 10），持续4周。接下来，对所有组进行程控电刺激以评估其对室性心律失常（VAs）的易感性。与ISO大鼠相比，给予dapa不仅有效降低了ISO处理大鼠的累积死亡风险、心肌纤维化、血浆血管紧张素II水平及其在心脏中的功能性受体AT1R蛋白表达，以及心脏组织中的促炎细胞因子水平，还改善了它们的心脏功能并抑制了氧化应激。这些作用与S/V相似。然而，在降低左心室舒张末期容积、降低心率和室性心律失常、减轻体重和降低血糖水平方面，dapa比S/V显示出更大的疗效。dapa对心肌病发挥保护作用的机制可能与其间接抗氧化能力和直接降糖作用有关。
