三种细胞因子对肺纤维化中纤维母细胞转分化的作用

Effect of cytokines on the trans-differentiation of fibroblasts in pulmonary fibrosis

目的观察大鼠肺纤维化形成过程中TGF-1β、PDGF-AA、PDGF-BB与肌纤维母细胞的标志物-αSMA在不同时间的表达量,探索细胞因子在纤维母细胞转分化为肌纤维母细胞过程中的作用及与肺纤维化程度的关系。方法气管内注射博莱霉素制备大鼠肺纤维化模型,分别在第7、14、28天处死大鼠取肺组织,应用HE和免疫组化方法观察大鼠肺纤维化程度和四个指标表达的动态变化。结果造模后纤维母细胞表达-αSMA在第7天最明显,以后渐降。TGF-β1在第7天表达明显增强,第14天最强,第28天明显降低。纤维母细胞和肺泡巨噬细胞表达PDGF-AA在第7天最强,以后渐降。PDGF-BB在纤维母细胞的表达与PDGF-AA相似,在肺泡巨噬细胞则第14天最强。结论Fb自分泌TGF-β1、PDGF-AA、PDGF-BB在其转分化中发挥主要作用。AM是PDGF、TGF-β1的重要来源,在肺泡炎和纤维化持续中发挥重要作用。

Objective To investigate the TGF-β1 , PDGF-AA, PDGF-BB and α-SMA expressions at different times on mrs with pulmonary fibrosis （PF）. Method The expressions of TGF-β1, PDGF-AA, PDGF-BB and α-SMA were determined by immunohistochemical methods. Results After bleomycin treatment, Fb showed the most positive reaction to anti-α-SMA on the 7th day, and then it significantly decreased. The expression of TGF-β1 continuously increased in the early and middle stages after bleomycin treatment （7-14 days）, but decreased in the late stage. The expression of PDGF-AA in Fb and AM was the highest on the 7th day, and then it gradually decreased. The positive staining for PDGF-BB in Fb was similar to that of PDGF-AA, but AM showed a strong positive staining on the 14th day. Conclusion TGF-β1 , PDGF-AA and PDGF-BB deriving from autocrine by Fb play primary roles on the trans-differentiation of fibroblasts. AM is an important source of TGF-β1 and PDGF.