Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Cardiovasc Pathol. 2022 Sep-Oct;60:107432. doi: 10.1016/j.carpath.2022.107432. Epub 2022 May 11.
Atrial fibrillation (AF) is closely associated with the overactivation of the renin-angiotensin-aldosterone system. Large cohort studies and recent meta-analyses have shown that the utilization of mineralocorticoid receptor antagonists has positive effects on the prevention and development of AF. This study aimed to investigate the effects of eplerenone on atrial remodeling in AF model rats and elucidate its intrinsic mechanism.
Ninety male Sprague-Dawley rats were randomly divided into the control group, chronic intermittent hypoxia (CIH) group, and CIH-eplerenone intervention (CIH-E) group. Rats in the CIH and CIH-E groups received CIH for 6 weeks, and rats in the CIH-E group were additionally administered eplerenone gavage (10 mg/kg/d). After modeling, the baseline parameters of each group were examined. Histopathology, molecular biology, isolated electrophysiology, and patch clamp experiments were performed after sampling.
Compared with the control group, rats in the CIH group showed atrial enlargement, significant aggravated fibrosis, upregulated JAK/STAT3 pathway, shortened effective refractory period (ERP), increased AF inducibility, and decreased peak current density of characteristic voltage-gated ion channels in atrial myocytes. After eplerenone intervention, rats in the CIH-E group had a smaller atrial diameter than those in the CIH group. Furthermore, downregulated JAK/STAT3 pathway, prolonged ERP, decreased AF inducibility, and increased peak current density of characteristic ion channels were also observed in the CIH-E group.
CIH induced significant atrial remodeling in rats and eplerenone significantly ameliorated the atrial remodeling caused by CIH. This could be attributed to the downregulation of the JAK/STAT3 pathway and the increase in the characteristic ion current density of atrial myocytes.
心房颤动（AF）与肾素-血管紧张素-醛固酮系统的过度激活密切相关。大量队列研究和最近的荟萃分析表明，利用盐皮质激素受体拮抗剂对 AF 的预防和发展有积极作用。本研究旨在探讨依普利酮对 AF 模型大鼠心房重构的影响，并阐明其内在机制。
90 只雄性 Sprague-Dawley 大鼠随机分为对照组、慢性间歇性低氧（CIH）组和 CIH-依普利酮干预（CIH-E）组。CIH 组和 CIH-E 组大鼠接受 CIH 6 周，CIH-E 组大鼠给予依普利酮灌胃（10mg/kg/d）。建模后，检测各组基础参数。取样后进行组织病理学、分子生物学、分离电生理学和膜片钳实验。
与对照组相比，CIH 组大鼠心房扩大，纤维化明显加重，JAK/STAT3 通路上调，有效不应期（ERP）缩短，AF 易感性增加，心房肌细胞特征电压门控离子通道峰值电流密度降低。依普利酮干预后，CIH-E 组大鼠心房直径小于 CIH 组。此外，CIH-E 组还观察到 JAK/STAT3 通路下调、ERP 延长、AF 易感性降低和特征离子通道峰值电流密度增加。
CIH 诱导大鼠发生明显的心房重构，依普利酮显著改善 CIH 引起的心房重构。这可能归因于 JAK/STAT3 通路的下调和心房肌细胞特征性离子电流密度的增加。
