X射线照射联合PD-1抑制剂对小鼠肺损伤的机制研究  

Mechanism study of X-ray irradiation combined with PD-1 inhibitor on lung injury in mice

作　　者：王欣雨 孙成龙 Wang Xinyu;Sun Chenglong(School of Medicine,Anhui University of Science and Technology,Huainan,Anhui 232001,China;Department of Radiotherapy,Anhui Second People's Hospital,Hefei,Anhui 230041,China)

机构地区：[1]安徽理工大学医学院,安徽淮南232001 [2]安徽省第二人民医院放疗科,安徽合肥230041

出　　处：《齐齐哈尔医学院学报》2025年第3期228-233,共6页Journal of Qiqihar Medical University

基　　金：安徽省教育厅自然科学研究重点项目(KJ2021A1270);安徽省教育厅自然科学研究重点项目(2022AH052322);安徽医科大学研究基金(2022XKJ250);安徽省重大疑难病症中西医结合协作研究项目(2021zdynjb10);安徽省中医药传承创新科研项目(2024cccx015)。

摘　　要：目的 明确X射线照射联合PD-1免疫检查点抑制剂给药对小鼠模型肺组织损伤的影响及其潜在机制。方法 将18只C57BL/6j小鼠随机分为对照组、照射组、照射联合PD-1抑制剂组三组,每组各6只。照射结束后28 d对肺组织进行病理组织染色,评估组织形态学和病理学变化。酶联免疫吸附法(ELISA)检测转化生长因子-β1(TGF-β1)和肿瘤坏死因子-α(TNF-α)水平。Western blot检测小鼠肺组织中核因子κB(NF-κB)信号通路相关蛋白的表达。结果 照射组肺损伤指标高于对照组。同时,照射联合PD-1抑制剂组小鼠肺炎、肺纤维化指数及肺组织p-IκBα和p-P65蛋白表达均高于其他两组。结论 全胸X射线照射联合PD-1抑制剂可加重小鼠肺损伤和肺纤维化,其作用机制可能与NF-κB信号通路有关。Objective To clarify the effects and potential mechanisms of X-ray irradiation combined with PD-1 immune checkpoint inhibitor administration on lung tissue injury in mouse models.Methods Eighteen C57BL/6j mice were randomly divided into three groups of six mice each:control group,irradiation group,and irradiation combined with PD-1 inhibitor group.Pathological tissue staining of lung tissues was performed 28 days after the end of irradiation to assess histomorphologic and pathological changes.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of transforming growth factor-β1(TGF-β1)and tumor necrosis factor-α(TNF-α).Western blot was used to detect the expression of proteins related to the nuclear factorκB(NF-κB)signaling pathway in the lung tissues of mice.Results The lung injury indexes of the irradiation group were higher than those of the control group.Meanwhile,the lung pneumonia,lung fibrosis index,and the expression of p-IκBαand p-P65 proteins were higher in the irradiation combined with PD-1 inhibitor group than in the other two groups.Conclusions Whole chest X-ray irradiation combined with PD-1 inhibitor could aggravate lung injury and lung fibrosis in mice,and its mechanism may be related to the NF-κB signaling pathway.

关 键 词：PD-1抑制剂 放射性肺损伤 肺纤维化 肺炎 NF-ΚB信号通路 

分 类 号：R730.55[医药卫生—肿瘤]