解放军医学院学报2025，Vol.46Issue(3)：239-246,255,9.DOI:10.12435/j.issn.2095-5227.25010103
索凡替尼通过抑制巨噬细胞M2型极化减轻小鼠放射性肺纤维化
Surufatinib attenuates radiation-induced pulmonary fibrosis in mice via suppression of macrophage M2 polarization
商庆超 1冯胜强 2张沛 3杜乐辉 3雷霄 3马娜 3张倩 3郭兴东 3曲宝林3
作者信息
- 1. 解放军医学院,北京 100853||解放军总医院第一医学中心放射治疗科,北京 100853
- 2. 解放军联合参谋部警卫局,北京 100000
- 3. 解放军总医院第一医学中心放射治疗科,北京 100853
- 折叠
摘要
Abstract
Background Radiation-induced lung injury represents the most critical dose-limiting toxicity in radiotherapy for thoracic malignancies.As a late-stage adverse effect,radiation-induced lung fibrosis currently lacks effective treatment options.Objective To investigate the therapeutic effects of surufatinib on radiation-induced lung fibrosis and the underlying mechanisms.Methods Ten 6-8-week-old male C57BL/6 mice were randomly divided into control group and treatment group,with 5 mice in each group.The treatment group received surufatinib(dosage:20 mg/kg;concentration:4 mg/mL)via oral gavage for 4 weeks,while the control group was administered an equivalent volume of saline using the same method.The toxicity of surufatinib was evaluated through H&E staining of tissues and serum biochemical analyses,including creatinine(CRE),blood urea nitrogen(BUN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),and creatine kinase-MB(CK-MB).Thirty 6-8 week-old male specific pathogen free-grade C57BL/6 mice were randomly divided into normal control group,irradiation group,and irradiation+surufatinib group.A mouse model of radiation-induced lung fibrosis was established with thoracic γ radiation at a single dose of 20 Gy.Irradiation+surufatinib group mice received surufatinib via oral gavage(20 mg/kg/day for 4 consecutive weeks;concentration:4 mg/mL)starting at week 8 post-irradiation.At 12 weeks after irradiation,the degree of lung fibrosis was evaluated using lung coefficient,H&E staining and Masson staining,and the expression levels of α-SMA and collagen I were detected using immunohistochemical staining.Total proteins were extracted from lung tissues,and the expression levels of Arg-1 and YM-1 were detected by Western blot.In vitro experiments,RAW264.7 cells and BMDMs were treated with surufatinib after the administration of IL-4 and IL-10.The expression levels of Arg-1 and YM-1 were determine by Western blot.Results In vivo experiments,no signs of toxicity were observed in mice treated with surufatinib according to histological analysis and biochemistry test.Histopathological analysis(H&E staining,Masson staining,and immunohistochemical staining)demonstrated that at 12 weeks post-irradiation,the irradiation group exhibited substantial collagen fiber deposition in lung tissues,accompanied by elevated lung index,α-SMA,and Collagen I expression.These pathological alterations were significantly ameliorated in the irradiation+surufatinib group(P＜0.001).The expression levels of Arg-1 and YM-1 were down-regulated in the irradiation+surufatinib group(P＜0.05).The CCK-8 assay results indicated that both types of macrophages exhibited a decrease in cell viability at a concentration of 4 μM.Experiments in vitro further confirmed that surufatinib inhibited the M2 polarization of macrophages induced by IL-4 and IL-10.Conclusion Surufatinib has a therapeutic effect on radiation-induced lung fibrosis in mice by inhibiting the polarization of macrophages to the M2 phenotype.关键词
放射性肺纤维化/索凡替尼/巨噬细胞/集落刺激因子1/集落刺激因子1受体Key words
radiation-induced lung fibrosis/surufatinib/macrophage/colony stimulating factor-1/colony stimulating factor receptor-1分类
医药卫生引用本文复制引用
商庆超,冯胜强,张沛,杜乐辉,雷霄,马娜,张倩,郭兴东,曲宝林..索凡替尼通过抑制巨噬细胞M2型极化减轻小鼠放射性肺纤维化[J].解放军医学院学报,2025,46(3):239-246,255,9.
