目的:探讨布地奈德(budesonide,BUD)对肺纤维化大鼠肺组织Ⅰ、Ⅲ型胶原mRNA表达以及支气管肺泡灌洗液(BALF)中TNF-α、TGF-β1、PDGF-BB、IFN-γ含量的影响。方法:取健康雌性Wistar大鼠随机分成博莱霉素(BLM)组、生理盐水(NS)组和BUD组,每组15只。BUD组、BLM组气管内灌注BLM,NS组气管内灌注NS,继之0~6d每天雾化1次,BUD组雾化吸入BUD,BLM组和NS组雾化吸入NS,各组分别于第7、14、28d处死大鼠各5只。用HE、Masson染色观察肺泡炎症和纤维化改变;反转录聚合酶链式反应(reverse transcription-PCR,RT-PCR)法测定肺组织Ⅰ、Ⅲ型胶原mRNA表达;酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法测定BALF中TNF-α、TGF-β1、PDGF-BB、IFN-γ含量。结果:BUD组第7、14d肺泡炎程度较BLM组减轻(P〈0.05),BUD组第7、14、28d肺纤维化程度均较BLM组减轻(P〈0.05);BUD组第7、14、28d肺组织Ⅰ、Ⅲ型胶原mRNA表达较BLM组明显降低(P〈0.05)。与BLM组比较,BUD组第7、14、28d BALF中TNF-α、TGF-β1、PDGF-BB含量较BLM组明显降低,IFN-γ含量增高(P〈0.05)。结论:BUD雾化吸入可减轻BLM致肺纤维化大鼠肺泡炎症,降低肺组织Ⅰ、Ⅲ型胶原mRNA表达及BALF中TNF-α、TGF-β1、PDGF-BB含量,可抑制BALF中IFN-γ含量下降,从而减轻纤维化程度。
Objective: To investigate the effect of Budesonide(BUD) on type Ⅰand Ⅲ collagen mRNA in lung tissue and TNF-α,TGF-β1,PDGF-BB,IFN-γ in BALF in rats with pulmonary fibrosis.Methods: 45 adult female Wistar rats were randomly divided into normal saline(NS) group,BUD group and bleomycin(BLM) group.Both BUD group and BLM group were instilled into the tracheas with BLM,and NS group with 0.9 % NaCl solution.Aerosol inhalation was performed in 3 groups once everyday at day 0~6(NS group and BLM group inhaled aerosolized NS;BUD group inhaled aerosolized BUD).5 rats in every group were sacriced at 7th,14th,28th day.The extent of alveolitis and fibrosis was observed in HE and Masson staining.The levels of type Ⅰ/ Ⅲcollagen mRNA in lung tissue were measured by RT-PCR.The concentration of TNF-α,TGF-β1,PDGF-BB,IFN-γ in BALF was measured by ELISA.Results: The extent of alveolitis in BUD group at 7th,14th day was significantly lower than those of BLM group(P〈0.05).The extent of fibrosis in lung tissue and the concentration of TNF-α,TGF-β1 and PDGF-BB in BALF in BUD group at 7th,14th,28th day was significantly lower than those in BLM group(P〈0.05);The levels of type Ⅰ/ Ⅲcollagen mRNA at 7th,14th,28th day in BUD group was significantly lower than those in BLM group(P〈0.05).However,the concentration of IFN-γ in BUD group at 7th,14th and 28th day was significantly higher than those of BLM group(P〈0.05).Conclusion: After inhaled BUD,the levels of type Ⅰ/Ⅲ collagen mRNA in lung tissue and the concentration of TNF-α、TGF-β1、PDGF-BB in BALF could be decreased,the concentration of IFN-γ in BALF could be increased,and the formation of pulmonary fibrosis could be suppressed in bleomycin-induced pulmonary fibrosis rats.