布地奈德对肺纤维化大鼠Smad4、PDGF-A及PAI-1表达的影响

Effect of Budesonide on Smad4,PDGF-A and PAI-1 in a rat model of pulmonary fibrosis

目的:探讨布地奈德(BUD)对肺纤维化大鼠肺组织转化生长因子-β1(TGF-β1)、血小板衍化生长因子-A(PDGF-A)、抗生物皮肤生长因子同源物4母体(Smad4)、纤溶酶原激活物抑制物-1(PAI-1)表达的影响。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。NS组气管内灌注NS,BUD组、BLM组气管内灌注BLM,继之0～6 d每天雾化1次,BLM组和NS组雾化吸入NS,BUD组雾化吸入BUD,分别于第7、14、28天处死3组大鼠各5只。用HE、Masson染色观察肺泡炎症和纤维化改变;免疫组化法测定肺组织中TGF-β1、PDGF-A、Smad4、PAI-1的表达。结果:第7、14天,BUD组肺泡炎程度较BLM组减轻(P<0.05);第7、14、28天,BUD组肺纤维化程度均较BLM组减轻(P<0.05)。第7、14、28天,BUD组肺组织中TGF-β1、PDGF-A、Smad4、PAI-1表达较BLM组明显降低(P<0.05)。结论:BUD雾化吸入可降低肺纤维化大鼠肺组织TGF-β1、PDGF-A、Smad4、PAI-1的表达,同时亦可减轻其肺泡炎及肺纤维化程度。

AIM： To observe the effect of Budesonide （BUD） on TGF-β1, PDGF-A, Smad4 and PAl-1 in lung tissue in pulmonary fibrosis rats. METHODS： Forty-five a- dult female Wistar rats were randomly divided into normal solution （NS） group, BUD group and bleomycin （BLM） group. 9 g/L NaCI solution was instilled into the tratrache- aes in NS group, and BLM were used in BUD group and BLM group. NS group and BLM group were inhaled with 9 g/L NaCI solution once everyday at day 0 -6, and BUD group were used with BUD. Five rats in every group were killed at 7th, 14th 28th day. The appearances of alveolitis and fibrosis were displayed in HE and Masson staining. The expressions of TGF-[51, PDGF-A, Smad4 and PAl-1 in lung tissue were detected by immunohistochemistry. RESULTS： The extent of the alveolitis in BUD group at ？th, 14th day were significantly lower than that in BLM group （ P 〈 0. 05 ）. The fibrosis and the expressions of TGF-β1, PDGF-A, Smad4 and PAI-1 in lung tissues at 7th, 14th, 28th day, BUD group were significantly lower than BLM group （P〈0.05）. CONCLUSION： After inhaled BUD, the expressions of TGF-β1, PDGF-A, Smad4 and PAId in lung tissue could be decreased, and the extent of alveolitis and pulmonary fibrosis could be improved in bleomycin-induced pulmonary fibrosis rats.