目的: 探究达格列净对急性心肌梗死小鼠心脏保护作用及其可能机制。方法: 将8周龄雄性ICR小鼠采用左前降支结扎构建急性心肌梗死模型,随机分成5组：（1）假手术组;（2）急性心肌梗死模型组;（3）达格列净治疗组;（4）缬沙坦治疗组;（5）达格列净联合缬沙坦治疗组。造模成功后,分别给予达格列净、缬沙坦或生理盐水灌胃,28天后测量小鼠左心室功能和结构指标、心肌梗死面积,评估心肌间质胶原、梗死区胶原体积分数等,并检测核苷酸结合结构域样受体蛋白3（NLRP3）及其相关因子表达。结果: 与模型组比较,达格列净和缬沙坦能明显改善急性心肌梗死小鼠的左心室结构和功能,减少心肌梗死面积,改善心肌梗死后心肌细胞形态,减少炎症细胞浸润,抑制心肌纤维化程度;显著降低心肌组织中NLRP3、白细胞介素-1β、白细胞介素-6的表达。但与单用缬沙坦相比,达格列净联合缬沙坦未能进一步改善急性心肌小鼠左心室结构和功能以及上述各项指标。结论: 达格列净可以改善急性心肌梗死小鼠左心室结构和功能。然而,与缬沙坦相比,达格列净联合缬沙坦治疗未能进一步改善左心室结构和功能。
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.
关键词
急性心肌梗死 /
达格列净 /
核苷酸结合结构域样受体蛋白3
Key words
acute myocardial infarction /
dapagliflozin /
nucleotide binding dome-like receptor protein 3
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基金
湖南省科技创新重点工程（2020SK1013）; 湖南省临床医疗技术创新引导项目（2020SK50922）; 国家自然科学基金（81900466）; 湖南省自然科学基金青年项目（2020JJ5307）
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