CAJ | 학술논문

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(5 mg/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<0.01).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.
목적 탐토폐조직내T세포급기전화생장인자β1(TGF-β1)/γ-간우소(IFN-γ)표체여폐간질섬유화적관계.방법 C57BL/6소서30지,수궤분위5조,즉정상대조조화박래매소1、2、3、4주조.채용기관내주사박래매소(5 mg/kg)건립섬유화모형,분별우조모후1、2、3、4주단두처사,류취각조소서폐조직,관찰폐포염화폐섬유화정도,류식세포의재단개세포수평검측CD4+、CD8+、CD3+/CD8-/IFN-γ+화CD3+/CD8-/TGF-β1+세포적빈솔.결과 박래매소조소서출현명현섬유화;여정상대조조상비,박래매소조폐조직CD4+명현증다,CD8+현저강저(P치균<0.01);박래매소조폐조직CD4+T세포래원IFN-γ수평저우정상대조조,이CD4+T세포래원TGF-β1수평현저증고우정상대조조(P치균<0.01);CD4+TGF-β1+/CD4+IFN-γ+비치진행성증고,여폐섬유화평분정정상관(r=0.683,P<0.01).결론 CD4+T세포래원IFN-γ여TGF-β1분별하조여상조,삼여폐섬유화.
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 TGP-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-γ and upregulation of TGF-β1in the lung T lymphocyte may play an important role in pulmonary fibrosis.