Zhang Qing-Qing, Li Guo-Qing, Zhong Yi, Wang Jie, Wang An-Ning, Zhou Xiao, Mao Xiao-Ming
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 68 ChangLe St., Nanjing, 210006, China.
Ther Adv Chronic Dis. 2020 Nov 25;11:2040622320974833. doi: 10.1177/2040622320974833. eCollection 2020.
Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice.
Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of , and mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting.
Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice.
Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.
长期暴露于过量糖皮质激素常常与一种特定的心肌病相关。恩格列净，一种钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，具有有益作用，因为它有助于降低住院患者的心力衰竭和心血管死亡率。本研究的目的是调查恩格列净对小鼠慢性高皮质醇血症诱导的心肌纤维化和心肌功能障碍的影响。
将6周龄雄性C57BL/6J小鼠随机分为对照组、皮质酮（CORT）组和恩格列净+CORT组。给药4周后，通过超声心动图评估心脏结构和功能，并采集外周血和组织样本。通过RT-PCR评估心脏组织中、和mRNA的表达，并通过蛋白质印迹分析信号转导和转录激活因子3（STAT3）和Toll样受体4（TLR4）蛋白表达。
恩格列净有效降低了CORT处理小鼠的体重、肝脏甘油三酯、内脏脂肪体积和尿酸。在CORT处理的小鼠中给予恩格列净后，左心室肥厚和心脏功能障碍得到显著改善，磷酸化的STAT3和TLR4减轻，心肌中的巨噬细胞浸润受到抑制。
恩格列净对与CORT相关的特定心肌病具有有益作用，结果提供了新的证据表明恩格列净可能是预防这种疾病的潜在药物。
