CpG-ODN减轻放射性肺纤维化的作用及机理

张超; 高福; 蔡建明

doi:10.11889/j.1000-3436.2018.rrj.36.020201

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CpG-ODN减轻放射性肺纤维化的作用及机理

辐射生物学与医学 | 更新时间：2021-12-10

- CpG-ODN减轻放射性肺纤维化的作用及机理
- Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis
- 辐射研究与辐射工艺学报 2018年36卷第2期
- 作者机构：
  
  1.中国人民解放军兰州总医院放疗科兰州 730050
  2.中国人民解放军海军军医大学放射医学教研室上海 200433
- 作者简介：
  
  [ "张超, 男, 1984年10月出生, 2014年于原解放军第二军医大学获得医学博士学位, 现工作于解放军兰州总医院放疗科, 主治医师, E-mail:chaozhang369@qq.com", "ZHANG Chao (Male) was born in October 1984, and received medical doctor's degree from The Second Military Medical University in 2014. Now he works in Department of Radiotherapy, Lanzhou General Hospital of PLA. attending doctor, E-mail:chaozhang369@qq.com" ]
  蔡建明, 博士, 教授, E-mail:cjm882003@gmail.com Ph.D. CAI Jianming, professor, E-mail: cjm882003@gmail.com
- 基金信息：
  
  国家自然科学基金青年科学基金项目(81501623)
- DOI：10.11889/j.1000-3436.2018.rrj.36.020201
  中图分类号：
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张超, 高福, 蔡建明. CpG-ODN减轻放射性肺纤维化的作用及机理[J]. 辐射研究与辐射工艺学报, 2018,36(2):020201-7.

Chao ZHANG, Fu GAO, Jianming CAI. Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis[J]. Journal of Radiation Research and Radiation Processing, 2018,36(2):020201-7.
张超, 高福, 蔡建明. CpG-ODN减轻放射性肺纤维化的作用及机理[J]. 辐射研究与辐射工艺学报, 2018,36(2):020201-7. DOI： 10.11889/j.1000-3436.2018.rrj.36.020201.

Chao ZHANG, Fu GAO, Jianming CAI. Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis[J]. Journal of Radiation Research and Radiation Processing, 2018,36(2):020201-7. DOI： 10.11889/j.1000-3436.2018.rrj.36.020201.

摘要

使用单次全肺照射至吸收剂量15 Gy的C57BL/6雌性小鼠建立放射性肺纤维化模型，连续20周观察照射小鼠的基本情况和大体肺组织变化，制作肺组织Masson染色切片，并进行Ashcroft纤维化评分和纤维化面积定量，采用ELISA法测定细胞因子TGF-β1的表达水平，免疫组化法检测肺组织内TGF-β1、TβR、磷酸化Smad 2/3和Smad 7蛋白的表达。实验结果显示，照射后给予CpG-ODN处理，能使小鼠肺组织损伤及纤维化程度减轻，Ashcroft评级降低2分，纤维化面积减少约11%，促纤维化细胞因子TGF-β1表达水平下降近1/2，肺组织内的TGF-β1、TβR和磷酸化Smad 2/3蛋白的表达皆出现不同程度降低，Smad 7蛋白的表达升高。这些结果提示CpG-ODN能通过降低促纤维化细胞因子TGF-β1的表达水平抑制TGF-β1/Smad依赖性纤维化信号通路，从而减轻放射性肺纤维。

Abstract

The whole thorax of C57BL/6 female mice was irradiated to a single absorbed dose of 15 Gy. The formation of radiation-induced pulmonary fibrosis (RIPF) was assessed by lung index, Masson staining, Ashcroft score, and collagen synthesis for 20 weeks after irradiation. TGF-β1 was measured by ELISA assay, and the major proteins in TGF-β1/Smad-dependent pathway, including TGF-β, TβR, phosphor-Smad 2/3, and Smad 7, were detected by immunohistochemistry staining. The results showed that RIPF formation was significantly reduced when CpG-ODN was administered to mice irradiated. Expression of TGF-β1, a profibrotic cytokine, remained at a lower level. In TGF-β1-Smad-dependent pathways, TGF-β1, TβR, and phosphor-Smad 2/3 were downregulated, while Smad 7 was upregulated. This suggested that CpG-ODN prevented RIPF. The mechanism might be associated with a reduction of profibrogenic cytokine TGF-β1 and inhibition of the fibrosis-related downstream TGF-β1-Smad-dependent pathway.

关键词

放射性肺纤维CpG-ODNTGF-β1Smad蛋白

Keywords

Radiation induced pulmonary fibrosisCpG-ODNTGF-β1Smad protein

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