放射性肺纤维化（RIPF）是胸部肿瘤放疗的常见副作用，目前尚无有效的预防和治疗方法。本研究旨在探讨甘草酸（GA）对RIPF的保护作用及其潜在机制。使用接受GA处理的RIPF小鼠模型，以确定GA对RIPF的影响。通过Treg细胞与MLE-12细胞或小鼠胚胎成纤维细胞的共培养，并进行GA或转化生长因子-β1（TGF-β1）抑制剂干预以阻断TGF-β1，研究GA缓解RIPF的机制。此外，将Treg细胞注入GA处理的RIPF小鼠体内以提高TGF-β1水平，验证TGF-β1和Treg细胞的作用。GA干预改善了小鼠放疗后肺组织结构损伤和胶原沉积，并抑制了Treg细胞浸润、TGF-β1水平、上皮间质转化（EMT）和肌成纤维母细胞转化（MFB）。研究发现，GA和TGF-β1抑制剂可以通过降低TGF-β1水平预防Treg细胞诱导的EMT和MFB转化。此外，在经GA处理的RIPF小鼠中再灌输Treg细胞会上调TGF-β1水平，并加重RIPF。因此，GA可以改善小鼠的RIPF，其相应机制可能与Treg细胞通过抑制TGF-β1诱导的EMT和MFB转化有关。因此，GA可能是RIPF临床治疗的有前景的治疗候选药物。 版权所有 © 2023 Elsevier Inc. 发表。

Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiotherapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism.A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of Treg cells with MLE-12 cells or mouse embryonic fibroblasts and intervention with GA or Transforming growth factor-β1 (TGF-β1) inhibitor to block TGF-β1 were conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-β1 levels was performed to verify the roles of TGF-β1 and Treg cells.GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-β1 levels, epithelial mesenchymal transition (EMT) and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-β1 inhibitor, by decreasing TGF-β1. Furthermore, reinfusion of Treg cells upregulated TGF-β1 levels and exacerbated RIPF in GA-treated RIPF mice.GA can improve RIPF in mice, and the corresponding mechanisms are maybe related to the inhibition of TGF-β1-induced EMT and MFB transformation by Treg cells. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.Copyright © 2023. Published by Elsevier Inc.