Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice

Lu QIAO; Jie LI; Jing ZHANG; Yonglai CHEN; Yuhui HAO

doi:10.16016/j.2097-0927.202212009

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Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice

Basic Medicine | 更新时间：2026-01-09

- Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice
- Journal of Army Medical University Vol. 45, Issue 9, Pages: 975-981(2023)
- 作者机构：
  
  400038 重庆, 陆军军医大学(第三军医大学)军事预防医学系复合伤研究所
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(2022NSCQ-MSX4675)
- DOI：10.16016/j.2097-0927.202212009
  CLC： R341;R563.9;R818.023
- Received：01 December 2022，
  
  Revised：2023-01-12，
  
  Published：15 May 2023
- 稿件说明：
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Lu QIAO, Jie LI, Jing ZHANG, et al. Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice[J]. Journal of Army Medical University, 2023, 45(9): 975-981.
DOI：

Lu QIAO, Jie LI, Jing ZHANG, et al. Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice[J]. Journal of Army Medical University, 2023, 45(9): 975-981. DOI： 10.16016/j.2097-0927.202212009.

摘要

目的

探讨血小板反应蛋白-1(thrombospondin-1

TSP-1)对放射性肺纤维化的影响及其可能机制。

方法

选取6~8周龄雄性野生型C57BL/6小鼠(wild type

WT)和全身性敲除TSP-1小鼠(TSP-1

-/-

)

将小鼠分为野生辐照组(WT+IR)和TSP-1敲除辐照组(TSP-1

-/-

+IR)

每组各6只。采用

Co γ射线全肺照射16 Gy建立放射性肺纤维化小鼠模型。照射后第16周

HE染色观察小鼠肺组织形态变化

天狼猩红染色观察肺组织胶原表达水平

qRT-PCR法检测小鼠肺组织中TGF-β1和Collagen Ⅰ的mRNA表达水平

micro-CT评价肺损伤和肺实变情况

FlexiVent系统评价小鼠肺功能水平

免疫荧光染色检测肺组织LC-3和p62的蛋白表达

透射电镜观察肺组织细胞自噬体。

结果

与野生辐照组相比

TSP-1敲除辐照组小鼠肺损伤减轻

肺组织胶原沉积减少

TGF-β1和Collagen Ⅰ的mRNA表达水平显著降低(

0.01)

肺功能水平有所改善。免疫荧光和透射电镜结果显示TSP-1敲除辐照组小鼠肺组织出现细胞自噬。

结论

TSP-1敲除能够减轻放射性肺纤维化

其机制可能与细胞自噬激活有关。

Abstract

Objective

To investigate the effect of thrombospondin-1(TSP-1) knockout on radiation-induced pulmonary fibrosis and explore its underlying mechanism.

Methods

Male wild type C57BL/6 mice (6~8 weeks old

WT mice) and TSP-1 knockout mice (TSP-1

-/-

mice) were subjected and received 16 Gy

Co γ-ray whole lung irradiation (IR) to induce radiation pulmonary fibrosis

and then

the mice were assigned into WT+IR group and TSP-1

-/-

+IR group

respectiv

ely

with 6 mice in each group.In 16 weeks after irradiation

HE staining was performed to observe the morphological changes in lung tissues

and Sirius red staining was used to observe the collagen expression in lung tissues.qRT-PCR was employed to detect the mRNA expression of TGF-β1 and Collagen Ⅰ in lung tissues.Micro-CT scanning was adopted to evaluate lung injury and substantial lung changes.FlexiVent system was employed to assess pulmonary function.Immunofluorescence staining was conducted to measure the protein levels of LC-3 and p62 in lung tissues.Transmission electron microscopy (TEM) was used to observe the cellular autophagic vesicles in lung tissues.

Results

Compared with the WT+IR group

the TSP-1

-/-

+IR group had reduced lung injury and collagen deposition in lung tissue

significantly lower mRNA levels of TGF-β1 and Collagen Ⅰ in lung tissue (

0.01)

and improved pulmonary function.Immunofluorescence assay and TEM showed that autophagy was observed in the mice of TSP-1

-/-

+IR group.

Conclusion

TSP-1 knockout can alleviate radiation-induced pulmonary fibrosis

which may be related to activation of autophagy.

关键词

Keywords

references

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