肺间质纤维化小鼠肺内T细胞γ-干扰素和转化生长因子β1的表达

Interferon-γ and transforming growth factor-β1-producing T lymphocytes in lung tissue of mice with pulmonary fibrosis

目的探讨肺组织内T细胞及其转化生长因子β1（TGF-β1）／γ-干扰素（IFN-γ）表达与肺间质纤维化的关系。方法C57BL／6小鼠30只，随机分为5组，即正常对照组和博莱霉素1、2、3、4周组。采用气管内注射博莱霉素（5mg／kg）建立纤维化模型，分别于造模后1、2、3、4周断头处死，留取各组小鼠肺组织，观察肺泡炎和肺纤维化程度，流式细胞仪在单个细胞水平检测CD4^＋、CD8^＋、CD3^＋／CD8^-／IFN-γ^＋和CD3＋／CD8^-／TGF-β1^＋细胞的频率。结果博莱霉素组小鼠出现明显纤维化；与正常对照组相比，博莱霉素组肺组织CD4^＋明显增多，CD8^＋显著降低（P值均〈0．01）；博莱霉素组肺组织CD4^＋T细胞来源IFN-γ水平低于正常对照组，而CD4^＋T细胞来源TGF-β1水平显著增高于正常对照组（P值均〈0．01）；CD4^＋TGF—β1^＋／CD4^＋IFN-γ^＋比值进行性增高，与肺纤维化评分呈正相关（r=0．683，P〈O．01）。结论CD4^＋T细胞来源IFN-γ与TGF-β1分别下调与上调，参与肺纤维化。

Objective To investigate the changes and significance of interferon-γ（IFN-γ） and transforming growth factor-β1 （TGF-β1） expression in lung T lymphocytes from mice with pulmonary fibrosis. Methods Thirty pathogen-free C57BL/6 mice were randomly divided into five groups： control group,bleomycin one-week group, bleomycin two-week group, bleomycin three-week group and bleomycin four-week group. Pulmonary fibrosis was induced by intratracheal injection of bleomycin （5 mg/kg）. Lungs were isolated one, two, three and four weeks after bleomycin treatment. Histological changes in the lungs were evaluated by haematoxylin-eosin stain or Masson trichrome stain, and scored. T cellular phenotypes and the intracellular production of interferon IFN-γ,TGF-β1 in CD4^＋T cells were determined by flow cytometry. Results Bleomycin treatment led to considerable pulmonary fibrotic changes. Compared with control group, a significant increase in the percentage of CD4^＋ T cells and a significant decrease in the percentage of CD8^＋ were observed in all bleomycin groups（all P 〈0.01）. With the progression of fibrosis, a significant increase in the percentage of TGF-β1-producing CD4^＋ T cells and a significant decrease in the percentage of IFN-γ- producing CD4^＋ T cells were also observed（all P 〈0.01）. There was positive correlation between the ratio of CD4^＋ TGF-β1 ＋/CD4^＋ IFN-γ＋ and the scores of pulmonary fibrosis（ r =0. 683, P 〈0.01）. Conclusions Downregulation of IFN-β1 and upregulation of TGF-β1 in the lung T lymphocyte may play an important role in pulmonary fibrosis.