Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.

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二甲双胍和纤维化：现有证据和机制的回顾

纤维化是对器官损伤的生理反应，其特征是器官中结缔组织成分的过度沉积，导致生理结构和器官重塑的破坏，最终导致器官衰竭和死亡。肺、肾和肝中的纤维化占全球残疾和死亡负担的很大一部分。迄今为止，没有控制纤维化的有效治疗策略。一类代谢靶向化学物质，例如一磷酸腺苷活化蛋白激酶 (AMPK) 激活剂和过氧化物酶体增殖物激活受体 (PPAR) 激动剂，在对抗纤维化方面显示出强大的潜力。二甲双胍是一种有效的 AMPK 激活剂，是唯一推荐用于治疗 2 型糖尿病的一线药物，已成为减少或逆转纤维化的一种有前途的方法。在这篇综述中，我们首先总结了专门研究二甲双胍对器官纤维化影响的关键实验和临床研究。然后，我们深入讨论了介导二甲双胍抗纤维化作用的机制。