成纤维细胞激活蛋白在小鼠肺纤维化模型中的表达

Expression of Fibroblast Activation Protein in Mouse Pulmonary Fibrosis Model

目的探讨成纤维细胞激活蛋白(FAP)在实验性小鼠肺纤维化组织中的表达,及其与α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)之间的相互关系。方法气管内滴入博莱霉素(7mg/kg)制备肺纤维化模型,采用免疫组化技术检测小鼠肺纤维化组织中FAP、α-SMA和TGF-β1的表达。结果正常肺组织无FAP表达;纤维化组FAP表达于细支气管和大血管周围的成纤维细胞,成纤维细胞灶中FAP、α-SMA和TGF-β1表达部位相似,但FAP比α-SMA的表达更广泛,比TGF-β1的表达更强。FAP、α-SMA和TGF-β1与小鼠肺纤维化程度均呈正相关(r值分别为0.795、0.766和0.628,P<0.01),且FAP与TGF-β1的表达呈正相关(r=0.706,P<0.01)。结论 FAP特异性表达在小鼠肺纤维化组织的成纤维细胞灶中,与肺纤维化程度有关。FAP与TGF-β1可能在肺纤维化形成中起协同作用。

Objective To investigate the expression of fibroblast activation protein（FAP） in mouse pulmonary fibrosis and the relationship between FAP and trarisforming growth factor β1（TGF-β1）.Methods The mouse model with pulmonary fibrosis was established by intratracheally instillation of bleomycin.The expressions of FAP,α-smooth muscle action（α-SMA）,and TGF-β1 in lung tissues were detected with immunohistochemical technique.Results There was no expression of FAP in the normal lung tissue.In the pulmonary fibrosis mice,FAP was found in the fibroblasts existed in bronchiolar adventitia or peribronchiolar（and perivascular） connective tissue.In the fibroblast foci,the localizations of α-SMA,TGF-β1,and FAP were similar,but the expression of FAP was more extensive than that of α-SMA and stronger than that of TGF-β1.The degree of lung fibrosis was strongly correlated with FAP,α-SMA,and TGF-β1（r=0.795,0.766,0.628;P0.01）.A significantly positive correlation was also observed between TGF-β1 and FAP（r=0.706,P0.01）.Conclusions FAP is especially expressed in the fibroblast foci in pulmonary fibrosis and strongly correlated with the severity of pulmonary fibrosis.FAP and TGF-β1 possibly play a synergistic role in the progression of pulmonary fibrosis.