Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8365-8370. doi: 10.3892/mmr.2017.7676. Epub 2017 Sep 29.
Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose‑dependently inhibited ISO‑induced CF proliferation in vitro. The ISO‑triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N‑acetylcysteine (NAC), and not affected by cardiotrophin‑1 (CT‑1) knockdown. In addition, AsIV effectively reversed ISO‑induced upregulation of CT‑1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen Ι overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT‑1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO‑induced CF proliferation and collagen production through negative regulation of ROS‑mediated CT‑1 upregulation.
黄芪甲苷（AsIV）是黄芪的主要活性成分之一，具有抗氧化活性，表现出显著的抗纤维化作用。心肌纤维化是心力衰竭相关心脏重构的重要病理机制。在本研究中，研究了 AsIV 对异丙肾上腺素（ISO）刺激的抗纤维化作用的机制。AsIV 显著改善了体内的心肌纤维化，并呈剂量依赖性抑制了体外 ISO 诱导的 CF 增殖。AsIV 显著抑制了 ISO 触发的活性氧（ROS）水平升高，以及 ROS 清除剂 N-乙酰半胱氨酸（NAC），而不影响心营养素-1（CT-1）的敲低。此外，AsIV 有效逆转了 ISO 诱导的 CT-1 表达上调，而 NAC 预处理则减弱了这种上调。AsIV、NAC 和 CT-1 小干扰 RNA 转染有效阻断了 ISO 刺激诱导的 CF 增殖和胶原Ⅰ过度表达。综上所述，这些结果表明，AsIV 通过负调控 ROS 介导的 CT-1 上调，有效抑制 ISO 诱导的 CF 增殖和胶原产生。
