Xiao Huijuan, Huang Xiaoxi, Wang Shiyao, Liu Zheng, Dong Run, Song Dingyun, Dai Huaping
Department of Respiratory Medicine, Capital Medical University Beijing 100054, P. R. China.
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital Beijing 100029, P. R. China.
Am J Transl Res. 2020 Mar 15;12(3):940-949. eCollection 2020.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease, which is characterized by the progressive deterioration in lung function. In the pathogenesis of IPF, insulin-like growth factor-1 (IGF-1) has been found to be heavily involved. Metformin, a commonly used oral antidiabetic agent, is known to inhibit IGF-1 by the reversal of hyperinsulinemia. In this study, we evaluated the effects of metformin in pulmonary fibrosis in C57/BL6J mice, and further understand the role of IGF-1 signaling pathway involving in this process. Pulmonary fibrosis was induced experimentally in these mice by the intratracheal injection of bleomycin (BLM). Metformin was given orally the day before or 14 days after bleomycin injection, while pirfenidone was used as the positive control. Our study showed that intratracheal injection of bleomycin induced pulmonary fibrosis in mice, with observed elevation in collagen, fibronectin and α-SMA level, characterized by the enhanced IGF-1 and PI3K expression. Metformin was able to inhibit these effects significantly, and its antifibrotic effect had no marked difference with pirfenidone. Our results show that metformin attenuates bleomycin-induced pulmonary fibrosis via IGF-1 pathway.
特发性肺纤维化（IPF）是一种毁灭性疾病，其特征是肺功能进行性恶化。在IPF的发病机制中，已发现胰岛素样生长因子-1（IGF-1）大量参与其中。二甲双胍是一种常用的口服抗糖尿病药物，已知可通过逆转高胰岛素血症来抑制IGF-1。在本研究中，我们评估了二甲双胍对C57/BL6J小鼠肺纤维化的影响，并进一步了解IGF-1信号通路在这一过程中的作用。通过气管内注射博来霉素（BLM）在这些小鼠中实验性诱导肺纤维化。在博来霉素注射前一天或注射后14天口服给予二甲双胍，而吡非尼酮用作阳性对照。我们的研究表明，气管内注射博来霉素可诱导小鼠肺纤维化，观察到胶原蛋白、纤连蛋白和α-平滑肌肌动蛋白水平升高，其特征是IGF-1和磷脂酰肌醇-3-激酶（PI3K）表达增强。二甲双胍能够显著抑制这些作用，并且其抗纤维化作用与吡非尼酮无明显差异。我们的结果表明，二甲双胍通过IGF-1途径减轻博来霉素诱导的肺纤维化。
