The Effect Of 16, 16-dimethyl Prostaglandin E2 On Bleomycin Induced Rat Pulmonary Fibrosis And Its Mechanism

Background and Objective: The study of pathogenesis of interstitial pulmonary fibrosis indicate that fibrosis and chronic inflammation rotate and promote each other in the injury progress with expression disorders of many cytokins and growth factors. Transforming growth factor- 1 (TGF- 1 )has been known as an important growth factor in lung fibrosis , Connective tissue growth factor(CTGF) is a downstream fibrogenic factor of TGF- , and it may play a critical role in the development of pulmonary fibrosis. Prosta- glandinE2(PGE2) can inhibit the fibroblast and myofibroblast expression of collagen protein induced by TGF- 1, it may be an inhibit factor in lung fibrosis. This experiment is to investigate the role of exogenous dmPGE2 in the progress of bleomycin-induced pulmonary fibrosis in rats ,observe the level of CTGFmRNA and the change of lung fibrosis.Materials and Methods: In this study, 63 Wisrar rats were divided into three groups in random: Control group,Model group, PGE2 group. Model group and PGE2 group were intratracheally instilled with bleomycin(5mg/kg body weight) and then PGE2 group treated with 16,16-dimethyl prostaglandin E2 1nmol/kg.d intradermicly until they were killed.. Treated Control group with the same volume of sterile saline. On day 7,14,28 after instillation, 7 rats of each group were sacrificed and the lung tissues were harvested for histopathological examination. The expression of CTGFmRNA, TGF- 1, collagen- I , collagen- III , cAMP dependent protein kinase(PKA) were measured by using in situ hybridization or SABC immunohistochemical technique.Results: (1) The expression of TGF- 1 of Model group on day 7 washighest, and all three stages were remarkably higher than Control group (P<0.05). (2)The expression level of TGF- β1 of PGE2 group on day 7 was lower than Model group, the difference is not remarkable(P>0.05),on 14and 28 day such level is significantly lower than Model group(P<0.05). (3)The activiation level of CTGF of Model group was largely higher than Control group and PGE2 group on day 7, 14, 28 (P<0.05). (4)The deposition of collagen-I , collagen-III of Model group on day 7, 14, 28 were remarkably increased compared with Control group and PGE2 group (P<0.05). (5)The expression of PKA of PGE2 group on day 7,14,28 were significantly higher than Model group(P<0.05).Conclusion: dmPGE2 can inhibit the progress of bleomycin-induced pulmonary fibrosis in rats. The probable pathogenesis is that it may inhibit the express of CTGF,then reduced deposition of collagen protein.