Departments of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Respiratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
Can J Physiol Pharmacol. 2021 Sep;99(9):885-893. doi: 10.1139/cjpp-2020-0662. Epub 2021 Jan 30.
Alamandine (ALA) and its receptor MrgD were recently identified as components of the renin-angiotensin system, which confer protection against cardio-fibrosis and renal-fibrosis; however, the effects of ALA on pulmonary fibrosis are unknown. This study was designed to serve two goals: () to evaluate the ALA/MrgD axis ability in the prevention of angiotensin II (Ang II) - induced pulmonary fibrosis in fibroblasts, and () to determine the effect of ALA in bleomycin (BLM) - treated C57B/6 mice. In vivo experiments revealed that the treatment of C57B/6 mice with ALA prevented BLM-induced fibrosis, and these findings were similar to those reported for pirfenidone. The antifibrosis actions of ALA were mediated via alleviation of oxidative injury and autophagy induction. In addition, in vitro studies revealed that ALA treatment attenuated Ang II-induced α-collagen I, CTGF, and α-SMA production in fibroblast which was blocked by D-Pro7-Ang-(1-7), a MrgD antagonist. This led to alleviation of oxidative injury and induction of autophagy similar to that reported for rapamycin. This study demonstrated that ALA via MrgD receptor reduced pulmonary fibrosis through attenuation of oxidative injury and induction of autophagy.
阿拉曼丁（ALA）及其受体 MrgD 最近被鉴定为肾素-血管紧张素系统的组成部分，该系统对心脏纤维化和肾脏纤维化具有保护作用；然而，ALA 对肺纤维化的影响尚不清楚。本研究旨在实现两个目标：（）评估 ALA/MrgD 轴在预防成纤维细胞中血管紧张素 II（Ang II）诱导的肺纤维化中的作用，和（）确定 ALA 在博来霉素（BLM）处理的 C57B/6 小鼠中的作用。体内实验表明，用 ALA 治疗 C57B/6 小鼠可预防 BLM 诱导的纤维化，这些发现与吡非尼酮的报道相似。ALA 的抗纤维化作用是通过减轻氧化损伤和诱导自噬来介导的。此外，体外研究表明，ALA 处理可减轻 Ang II 诱导的成纤维细胞中 α-胶原 I、CTGF 和 α-SMA 的产生，这一作用被 MrgD 拮抗剂 D-Pro7-Ang-(1-7) 阻断。这导致了与雷帕霉素相似的氧化损伤减轻和自噬诱导。本研究表明，ALA 通过 MrgD 受体减少肺纤维化是通过减轻氧化损伤和诱导自噬来实现的。
