Yu Jing, Zhao Huanhuan, Qi Xin, Wei Liping, Li Zihao, Li Chunpeng, Zhang Xiaoying, Wu Hao
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.
Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.
Front Pharmacol. 2021 Sep 23;12:730623. doi: 10.3389/fphar.2021.730623. eCollection 2021.
The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism. Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed . The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules. After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. , DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both and experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy. Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.
本研究旨在探讨钠-葡萄糖协同转运蛋白2抑制剂达格列净（DAPA）对缓解心肌肥厚的作用及其潜在分子机制。观察了以25mg/kg/d的剂量在饮用水中给予达格列净12周对小鼠腹主动脉缩窄（AAC）诱导的心肌肥厚的影响。采用超声心动图检测心脏功能变化，包括左室射血分数（LVEF）、左室短轴缩短率（LVFS）、左室舒张末期内径（LVEDd）、左室收缩末期内径（LVEDs）、心率（HR）和左室质量。通过Masson三色染色和麦胚凝集素（WGA）染色评估组织形态学变化。通过基因芯片分析处理后差异基因和信号通路的富集情况，观察血管紧张素II（AngII，2μM）诱导心肌细胞肥大及达格列净（1μM）的保护作用。通过心肌肌钙蛋白I（cTnI）免疫荧光染色检测心肌细胞的形态变化。采用酶联免疫吸附测定（ELISA）和定量逆转录聚合酶链反应（qRT-PCR）检测心肌肥厚相关分子的表达水平。治疗12周后，DAPA显著改善AAC诱导小鼠的心脏功能并抑制心肌肥厚。此外，DAPA显著抑制AngII诱导的心肌细胞异常肥大。两项实验均证实DAPA可介导磷脂酰肌醇5（Plin5）/过氧化物酶体增殖物激活受体α（PPARα）信号轴在抑制心肌肥厚中发挥保护作用。达格列净激活Plin5/PPARα信号轴并对心肌肥厚发挥保护作用。
