Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis

Chao ZHANG; Fu GAO; Jianming CAI

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

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Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis

RADIOBIOLOGY AND RADIOMEDICINE | 更新时间：2021-12-10

- Effects and mechanism of CpG-ODN ameliorating radiation induced pulmonary fibrosis
- Journal of Radiation Research and Radiation Processing Vol. 36, Issue 2, (2018)
- 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：
- 基金信息：
  
  National Natural Science Foundation Youth Science Project of China(81501623)
- DOI：10.11889/j.1000-3436.2018.rrj.36.020201
  CLC：
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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 36(2):020201-7(2018)
DOI：

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 36(2):020201-7(2018) 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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