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The Effect Of Fluvastain On ERK Cascade In Bleomycin-induced Intersitial Pulmonary Fibrosis Rats Models

Posted on:2006-03-09Degree:MasterType:Thesis
Country:ChinaCandidate:F XuFull Text:PDF
GTID:2144360182468048Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Bcakground and Objective: Interstitial pulmonary fibrosis is a kind of increased complicated disease, it is characterized with myofibroblast hyperplasia and deposition of collagen protein. Study demonstrated that extracellular signal regulated kinase (ERK) can regulate the expression of all kinds of cytokines , signal protein or growth factors, who plays a key role in the process of myofibroblast hyperplasia and deposition of collagen protein. Study demonstrated 3-hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors, HRI, not only play down hyperlipidemia but also inhibit cell proliferation and reduce deposition of collagen protein. In this experiment we use Fluvastain intervene bleomycin-induced intersitial pulmonary fibrosis rats models, to observe the expression and activity of extracellular signal regulated kinase (ERK) and investigate the effect of Fluvastain on the mechanism of bleomycin-induced intersitial pulmonary fibrosis.Materials and Methods: 60 Wistar rats were divided three groups: control group , model group and treatment group in random. On experimental day , the rats were intratracheally instilled with bleomycin(5mg/kg body weight)or sterile saline, and then treated with the Fluvastain and saline until they were killed .5 rats of every group were executed in 7,14,28,42 day. Immunohistochemistry and Westernblotting were used to measure the expression of TGF-β, ERK1/2 p-ERK protein.Results: (1) Lung coefficient in model group were increased remarkably compared with control group and treatment group(P≤0.05); (2) The degrees of alveolitis of treatment group were decreased on 7,14,28 than model group, and pulmonary fibrosis were decreased on 14,28,42(P≤0.05); (3)By Immunohistochemistry ERK1/2 p-ERK protein levels were increased in lung tissue of model rats compared with controls rats on 7,14,28,42(P≤0.05). ERK1/2 p-ERK protein levels were decreased in lung tissue of treatment group rats compared with model rats on 7 and 14, but, on day 28 and 42 , thedifference is not remarkable( P > 0.05); (4)TGF-|31evels were decreased in lung tissue of treatment group rats compared with model rats on 7 ,14 and 28, but, on day 42 , the difference is not remarkable( P > 0.05); (5)By Westernblotting ERKm p-ERK protein levels were decreased in lung tissue of treatment group rats compared with model rats on 7 ,14,28 and 42 , the difference is remarkable on day 7.Conclusion: Overexpression of ERK may play an important role in the development of IPF. Fluvastain can inhibit the progress of bleomycin-induced intersitial pulmonary fibrosis rats models, which pathogenesis is associated with decreasing the expression and activity of ERK protein.
Keywords/Search Tags:IPF, ERK, Fluvastain, Immunohistochemistry, Westernblotting
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