为了确定X射线照射联合PD-1免疫检查点抑制剂在小鼠模型中对肺组织损伤的影响及其潜在机制。总体上，将20只C57BL/6J小鼠随机分为四组，每组五只：对照组、PD-1抑制剂组、照射组和照射联合PD-1抑制剂组。辐射结束后30天，对肺组织进行苏木精-伊红染色以评估组织的形态和病理学变化。使用马兹氏染色和羟脯氨酸分析评估肺纤维化程度。酶联免疫吸附分析（ELISA）评估转化生长因子β1（TGF-β1）和肿瘤坏死因子α（TNF-α）的水平。通过免疫组化检测肺组织中的CD3+、CD4+和CD8+ T淋巴细胞。通过Western blotting评估肺组织中TGF-β1、Smad3、cGAS和STING的表达水平。照射组的肺损伤评分和肺纤维化指数均高于对照组。与其他三组相比，照射联合PD-1抑制剂组的肺炎评分、肺纤维化指数、CD4+细胞百分比和TGF-β1、p-Smad3和STING的表达在肺组织中更高。全胸腔X射线照射诱导小鼠肺损伤和肺纤维化，而PD-1抑制剂能够加重小鼠肺损伤和肺纤维化。因此，放射治疗联合PD-1抑制剂可能通过激活TGF-β1/Smad3和cGAS/STING信号通路，影响小鼠肺组织中的免疫炎症微环境，从而加重辐射诱导的肺组织损伤。版权所有 © 2023 The Authors。由Elsevier B.V.出版发行。保留一切权利。

To determine the effect of X-ray irradiation combined with PD-1 immune checkpoint inhibitor administration on lung tissue injury in a mouse model and its potential mechanism.In all, 20 C57BL/6J mice were randomly divided into four groups with five mice in each group: control group, PD-1 inhibitor group, irradiation group, and irradiation combined with PD-1 inhibitor group. Hematoxylin-eosin staining of the lung tissue was performed 30 days after the end of irradiation to evaluate the morphological and pathological changes in the tissue. Masson staining and analysis of hydroxyproline were used to evaluate the degree of pulmonary fibrosis. The levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor α(TNF-α) were evaluated by Enzyme-Linked immunosorbent assay (ELISA). CD3+, CD4+, and CD8+ T lymphocytes in the lung tissue were detected by immunohistochemistry. The expression levels of TGF-β1, Smad3, cGAS, and STING in the lung tissue were evaluated by Western blotting.The lung injury scores and pulmonary fibrosis indices in the irradiation group were higher than those in the control group. Meanwhile, lung pneumonia score, pulmonary fibrosis index, percentage of CD4 cells and expression of TGF-β1, p-Smad3, and STING in the lung tissue of mice in irradiation combined with PD-1 inhibitor group were higher than those in the other three groups.Lung injury and pulmonary fibrosis were induced by whole chest X-ray irradiation in mice, and PD-1 inhibitor could aggravate lung injury and pulmonary fibrosis in mice. Thus, radiotherapy combined with PD-1 inhibitors may affect the immune inflammatory microenvironment in the lung tissues of mice by activating TGF-β1/Samd3 and cGAS/STING signaling pathways, thus aggravating lung tissue damage induced by radiation.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.