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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2023, Vol. 16 ›› Issue (05) : 630 -634. doi: 10.3877/cma.j.issn.1674-6902.2023.05.005

论著

颗粒酶B激活TGF-β1/Smad3通路促进博来霉素导致的肺纤维化
陈向军, 顾兴, 王在强, 王光辉, 王莉, 方芳, 金发光, 王瑞璇†()   
  1. 710100　西安，西安市胸科医院重症医学二科
    710100　西安，西安市胸科医院呼吸与危重症医学科
    710038　西安，空军军医大学第二附属医院呼吸与危重症医学科
  • 收稿日期:2023-01-13 出版日期:2023-10-25
  • 通信作者: 王瑞璇
  • 基金资助:
    陕西省重点研发计划(2018ZDCXL-SF-02-03-02)

Granzyme B promotes bleomycin-induced pulmonary fibrosis by activating TGF-β1/Smad3 pathway

Xiangjun Chen, Xing Gu, Zaiqiang Wang, Guanghui Wang, Li Wang, Fang Wan, Faguang Jin, Ruixuan Wang†()   

  1. The second Department of Intensive Care Medicine, Xi′an Chest Hospital, Xi′an 710100, China
    Department of Respiratory and Critical Care Medicine, Xi′an Chest Hospital, Xi′an 710100, China
    Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi′an 710038, China
  • Received:2023-01-13 Published:2023-10-25
  • Corresponding author: Ruixuan Wang
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陈向军, 顾兴, 王在强, 王光辉, 王莉, 方芳, 金发光, 王瑞璇. 颗粒酶B激活TGF-β1/Smad3通路促进博来霉素导致的肺纤维化[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 630-634.

Xiangjun Chen, Xing Gu, Zaiqiang Wang, Guanghui Wang, Li Wang, Fang Wan, Faguang Jin, Ruixuan Wang. Granzyme B promotes bleomycin-induced pulmonary fibrosis by activating TGF-β1/Smad3 pathway[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(05): 630-634.

目的

分析颗粒酶B在博来霉素导致大鼠肺纤维化中的作用。

方法

将21只SD大鼠随机分为三组：对照组、模型组、干预组，每组7只。模型组和干预组采用经气管内注入博来霉素(5 mg/kg)诱导大鼠肺纤维化动物模型。干预组在造模前1 h、造模第7天、第14天和第21天经尾静脉注射颗粒酶B抑制剂，其它两组经尾静脉注射等体积生理盐水，其余操作相同。28 d后处死大鼠取出肺脏，采用免疫荧光和Western blot检测颗粒酶B、胶原蛋白I、转化生长因子β1(transforming growth factor β1)和Smad3蛋白表达情况，采用Masson染色检测肺组织纤维化情况。

结果

模型组较对照组大鼠肺组织胶原蛋白Ⅰ表达上调，胶原蛋白沉积增加，肺纤维化加重。干预组较模型组胶原蛋白Ⅰ表达下调，胶原蛋白沉积减少，肺纤维化减轻。模型组较对照组大鼠肺组织TGF-β1和Smad3蛋白表达增加，干预组较模型组TGF-β1和Smad3蛋白表达降低。

结论

颗粒酶B促进了博来霉素导致的大鼠肺纤维化，机制可能与激活TGF-β1/Smad3信号通路有关。

关键词: 肺纤维化, 颗粒酶B, 转化生长因子β1, Smad3
Objective

To explore the role of granzyme B in bleomycin-induced pulmonary fibrosis in rats.

Methods

21 SD rats were randomly divided into three groups: control group, model group and intervention group, with 7 rats in each group. The model group and the intervention group were injected with bleomycin (5 mg/kg) through the trachea to induce pulmonary fibrosis. The intervention group was injected with granzyme B inhibitor through caudal vein 1 hour before modeling, on day 7, 14 and 21, and the other two groups were injected with equal volume of normal saline. The remaining operations were the same. After 28 days, the rats were killed and the lungs were removed. The protein expressions of granzyme B, collagen I, TGF-β1 and Smad3 were detected by immunofluorescence and Western blot, and the pulmonary fibrosis was detected by Masson staining.

Results

Compared with the control group, collagen I expression, collagen deposition and pulmonary fibrosis were up-regulated in the model group. Compared with model group, collagen I expression was down-regulated, collagen deposition was reduced and pulmonary fibrosis was alleviated in the intervention group. The protein expressions of TGF-β1 and Smad3 in lung tissue of model group were increased compared with that of control group, while the protein expressions of TGF-β1 and Smad3 in intervention group were decreased compared with that of model group.

Conclusion

Granzyme B can promote bleomycin-induced pulmonary fibrosis in rats, and the mechanism may be related to the activation of TGF-β1/Smad3 signaling pathway.

Key words: Pulmonary fibrosis, Granzyme B, TGF-β1, Smad3
图1 各组大鼠肺组织Masson染色结果
图2 各组大鼠肺组织胶原蛋白I表达情况
图3 免疫荧光显示各组大鼠肺组织中颗粒酶B表达情况
图4 各组大鼠肺组织颗粒酶B、TGF-β1和Smad3蛋白表达情况
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