二甲双胍干预肺纤维化发病机制的研究进展

Research progress of metformin in the pathogenesis of pulmonary fibrosis

肺纤维化是一种慢性、进行性和不可逆的呼吸系统疾病,其特征是细胞外基质过度沉积导致炎症和广泛的肺重塑。目前尚无有效的治疗方法。多项研究表明二甲双胍是一种具有抗纤维化潜力的经典抗血糖药物。但目前关于二甲双胍发挥抗纤维化作用的具体机制尚未达成共识,本文就近几年来二甲双胍在肺纤维化领域的研究进展进行综述,主要从IGF-1/IGF-1R/PI3K信号、AMPK/mTOR信号、TGF-β/Smad信号通路以及干预肌成纤维细胞增殖和凋亡、改善氧化应激、抑制上皮间质转化及转谷氨酰胺酶2多种途径展开讨论,以期未来能够更深入和全面地理解二甲双胍抗纤维化机制与临床应用范围,为肺纤维化治疗提供新的思路。

Pulmonary fibrosis is a chronic,progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling.There is currently no effective treatment.Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential.However,at present,there is no consensus on the specific mechanism of metformin’s anti-fibrosis effect,and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years,mainly from IGF-1/IGF-1R/PI3K signaling,AMPK/mTOR signaling,TGF-β/Smad signaling pathway,and intervening in myofibroblast proliferation and apoptosis,improving oxidative stress,inhibiting epithelial interstitial transformation and transglutaminase.In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future,and provide new ideas for the treatment of pulmonary fibrosis.