Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Biomed Pharmacother. 2019 Oct;118:109243. doi: 10.1016/j.biopha.2019.109243. Epub 2019 Jul 23.
Myocardial remodeling is the key step in the development of ischemic cardiomyopathy. We aimed to compare effects of renal denervation (RDN) with those of angiotensin receptor neprilysin inhibitors (ARNi) on cardiac remodeling after myocardial infarction (MI), and explore underlying mechanism.
Sprague-Dawley rats (n = 40; male) were subjected to ligation of left anterior descending coronary artery to induce MI; six rats served as controls. ARNi was administered at a dose of 60 mg/kg/day for 4 weeks starting 1 week after MI. An RDN/Sham-RDN procedure was performed 1 week after MI. Rats in all groups were studied 5 weeks after MI. Echocardiography was used to evaluate cardiac function. Masson staining and TUNEL staining were used to determine the extent of cardiac remodeling. Indicators of oxidative stress in heart and brain were used to analyze the potential mechanisms involved.
Five weeks after MI, both RDN and ARNi significantly improved cardiac function and cardiac remodeling; however, RDN was superior to ARNi at attenuating myocardial apoptosis. Compared to ARNi, RDN was also more effective at decreasing the abnormal oxidative stress caused by MI; this was especially true in case of the brain and was confirmed by evaluating the changes in reactive oxygen species (ROS) levels and other oxidative stress parameters following MI.
RDN is not inferior to ARNi with respect to the improvement of cardiac remodeling in rats with ischemic cardiomyopathy. The effect of RDN might be associated with effective inhibition of oxidative stress in both the heart and brain.
心肌重构是缺血性心肌病发展的关键步骤。我们旨在比较肾去神经支配（RDN）与血管紧张素受体脑啡肽酶抑制剂（ARNi）对心肌梗死后心脏重构的影响，并探讨其潜在机制。
将 40 只雄性 Sprague-Dawley 大鼠结扎左前降支冠状动脉以诱导心肌梗死；其中 6 只大鼠作为对照。在心肌梗死后 1 周开始给予 ARNi 治疗，剂量为 60mg/kg/天，持续 4 周。在心肌梗死后 1 周进行 RDN/假手术-RDN 处理。所有组大鼠均在心肌梗死后 5 周进行研究。超声心动图用于评估心功能。Masson 染色和 TUNEL 染色用于确定心脏重构的程度。心脏和大脑中的氧化应激指标用于分析潜在的机制。
心肌梗死后 5 周，RDN 和 ARNi 均显著改善心功能和心脏重构；但 RDN 在减轻心肌细胞凋亡方面优于 ARNi。与 ARNi 相比，RDN 还能更有效地减轻由 MI 引起的异常氧化应激；在大脑中尤其如此，并通过评估 MI 后活性氧（ROS）水平和其他氧化应激参数的变化得到证实。
在改善缺血性心肌病大鼠的心脏重构方面，RDN 并不逊于 ARNi。RDN 的作用可能与有效抑制心脏和大脑中的氧化应激有关。
