Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

特发性肺纤维化（IPF）是一种原因不明的慢性进行性纤维化间质性肺炎。发病率逐年上升，无法治愈，预后较差。最近，磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（PKB/AKT）信号通路被认为是IPF的主要调节因子。PI3K/AKT 在纤维化过程中的贡献越来越突出，PI3K/AKT 抑制剂目前正在 IPF 中进行临床评估。因此，PI3K/AKT 代表纤维发生过程中的关键信号传导节点，对新型抗纤维化策略的开发具有潜在意义。本综述概括了对 IPF 病因的复杂解释所取得的进展，并证明 PI3K/AKT 可以最大程度地直接参与 IPF 的形成或与其他途径协同促进纤维化的发展。我们进一步总结了有前景的具有IPF治疗益处的PI3K/AKT抑制剂，包括处于临床试验和临床前研究中的抑制剂以及天然产物，并讨论了这些抑制剂如何减缓纤维化进展，以探索可能的潜在药物，这将有助于制定有效的治疗策略IPF 在不久的将来。