The Experimental Study On The Mechanisms Of Heme Oxygenase-1 In Pulmonary Fibrosis

Objective Heme oxygenase-1(HO-1)is an inducible stress protein1 In addition to its physiological role in heme degradation,HO-1 plays two-way important biological roles.This experiment is to study the effect of heme oxygenase-1(HO-1)on patho-physiological changes of bleomycin (BLM)induced pulmonary fibrosis in SD rat,and to investigate the mechanisms of HO-1 in the pathogenesis of pulmonary fibrosis.Methode Healthy SD rats(n=60)were random divided into a normal sodium(NS)group,a BLM group and an inhibitor of heme oxygenase-1-zinc protoporphyrin(Znpp)group.The pulmonary fibrosis model in BLM group and Znpp group was established by bleomycin.Five rats were sacrificed in each group respectively at 7,14,21,28 day.The HO-1 gene expression in lung tissue was detected by RT-PCR.The pathological changes of lung tissue by hematoxylin-eosin staining were investigated. The cell counting and neutrophil percentage,the level of total bilirubin and transforming growth factor-β1(TGF-β1)in the bronchoalveolar lavage fluid(BALF)and the content of reduced glutathione(GSH)and hydroxyproline(HYP)in the lung tissue were tested.Results(1)The HO-1 gene expression tested by RT-PCR in lung tissue of the BLM group is much more evident than that of the NS group and the Znpp group.(2)The difference of inflammation in HE staining between the BLM group and the Znpp group was not significant at the early stage,but at the later stage the fibrosis of the BLM group was more evident than that of the Znpp group.There were not inflammation and fibrosis in NS group.(3)The cell counting and neutrophil percentage of the BLM group and the Znpp group in the BALF was significantly higher than that of the NS group,but the experiment showed no significant different within the two groups.(4)The content of HYP of the BLM group in the lung tissue was significantly higher than that of the Znpp group and NS group,but the content of GSH was significantly lower than that of the Znpp group and NS group.(5)The level of TGF-β1 and total bilirubin of the BLM group in the BALF was significantly higher than that of the Znpp group and NS group.Conclusions The mechanisms of HO-1 in the pathogenesis of BLM induced pulmonary fibrosis in rat are those it can oxidize,damage and fiberize,but not inflame the lung issue.