Department of Cardiology, Suqian Hospital Affiliated of Xuzhou Medical University, 380 Huanghe South Road, Suqian, 223800, Jiangsu, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Amino Acids. 2021 Jul;53(7):1079-1089. doi: 10.1007/s00726-021-03005-8. Epub 2021 Jun 5.
The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague-Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dt) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-β were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-β expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.
本研究旨在探讨铃蟾素是否可以通过抑制氧化应激来缓解心力衰竭（HF）和减轻心肌纤维化。用血管紧张素（Ang）II 诱导心脏成纤维细胞（CFs）纤维化。结扎左前降支诱导 Sprague-Dawley 大鼠缺血性心肌梗死（MI）建立 HF 模型。通过腹腔注射铃蟾素（1.0 nM/kg/d）治疗 28 天。铃蟾素处理可改善 MI 大鼠左心室（LV）射血分数（EF）、缩短分数（FS）、LV 压力最大一阶导数（LV ± dp/dt）和 LV 收缩压（LVSP）的降低，LV 收缩期容积（LVVS）、LV 舒张期容积（LVVD）、LV 收缩末期直径（LVESD）和 LV 舒张末期直径（LVEDD）的增加。铃蟾素处理可抑制 MI 大鼠 CFs 和心脏中胶原 I、胶原 III 和转化生长因子（TGF）-β表达水平的增加。铃蟾素可逆转 Ang II 处理的 CFs 中 NADPH 氧化酶（Nox）活性、超氧阴离子和丙二醛（MDA）水平增加，以及超氧化物歧化酶（SOD）活性降低。Nox1 过表达逆转了铃蟾素对 Ang II 诱导的 CFs 胶原 I、胶原 III 和 TGF-β表达水平增加的抑制作用。这些结果表明，铃蟾素通过抑制 HF 大鼠氧化应激改善 HF 和心肌纤维化。Nox1 在调节铃蟾素对 Ang II 诱导的 CFs 纤维化的抑制作用中起重要作用。
