Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB R2H 2A6, Canada.
Molecules. 2021 Aug 18;26(16):5006. doi: 10.3390/molecules26165006.
The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.
心肌梗死后心力衰竭（HF）的发展和进展即使在目前的最佳治疗下也是一个主要问题。白藜芦醇是一种具有心脏保护作用的植物多酚。已知沙库比曲缬沙坦在慢性 HF 患者中有益。在这项研究中，我们研究了白藜芦醇与沙库比曲缬沙坦联合活性对照缬沙坦在 MI 诱导的雄性 Sprague Dawley 大鼠中的比较和组合益处。MI 诱导和假手术动物接受载体、白藜芦醇、沙库比曲缬沙坦、缬沙坦单独或沙库比曲缬沙坦+白藜芦醇 8 周。在终点进行超声心动图检查以评估心脏结构和功能。测量心脏氧化应激、炎症、纤维化、脑钠肽（BNP）、肌酐和中性粒细胞明胶酶相关脂质运载蛋白。白藜芦醇、沙库比曲缬沙坦、缬沙坦和沙库比曲缬沙坦+白藜芦醇治疗可显著防止 LV 扩张并改善 MI 诱导大鼠的 LV 射血分数。所有治疗还显著降低了心肌组织氧化应激、炎症和纤维化以及 BNP。沙库比曲缬沙坦和白藜芦醇联合治疗没有显示出附加效果。总之，白藜芦醇、沙库比曲缬沙坦和缬沙坦可显著防止 MI 诱导大鼠的心脏重构和功能障碍。MI 诱导大鼠心脏重构和功能障碍的减少是通过减少心脏氧化应激、炎症和纤维化来介导的。
