Dapagliflozin Improve Left Ventricular Structure and Function in Mice with Acute Myocardial Infarction
TANG Yi1, ZHU Wenyu1, TAN Siyuan1, ZHANG Min1, XU Xiaoping2, WANG Jiarui3, PENG Jianqiang1
1. Department of Cardiology, Hunan Provincial People's Hospital / The First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center of Heart Failure of Hunan Province, Changsha 410005, China; 2. Department of Gastroenterology, Hunan Provincial People's Hospital / The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China; 3. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Abstract:Objective To explore the cardioprotective role of dapagliflozin on acute myocardial infarction mice and its possible mechanism. Methods Eight-week-old male ICR mice were used to construct an acute myocardial infarction model by ligation of the left anterior descending coronary artery and were randomly divided into five groups: (1) Sham group, (2) Model group: acute myocardial infarction group, (3) DAPA group: dapagliflozin treatment group, (4) VAL group: valsartan treatment group; (5) DAPA+VAL group: dapagliflozin combined with valsartan treatment group. After successful modeling, mice were given dapagliflozin valsartan or normal saline by intragastric administration. After 28 days, left ventricular function and structural indexes were measured, myocardial infarct size was measured, myocardial interstitial collagen and collagen volume fraction in infarct area were evaluated, and the expression of nucleotide binding dome-like receptor protein 3(NLRP3) and its related factors were detected. Results Compared with the Model group, dapagliflozin and valsartan significantly improved left ventricular structure and function, reduced myocardial infarct area, improved myocardial cell morphology, reduced inflammatory cell infiltration, and inhibited myocardial fibrosis in mice with myocardial infarction. Meanwhile, dapagliflozin and valsartan significantly decreased the expression of NLRP3, interleukin-1β, interleukin-6 in myocardial tissue. However, compared with valsartan alone, dapagliflozin combined with valsartan failed to further improve left ventricular structure and function after acute myocardial infarction as well as the indices mentioned above. Conclusion Dapagliflozin can improve left ventricular structure and function. However, the combination of dapagliflozin and valsartan did not further improve left ventricular structure and function compared with valsartan alone.
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