The Effects Of N-acetylcysteine On The Expression Of HSP47 In The Pulmonary Fibrosis Induced By Bleomycin In Rats

Objectives To investigate the expression and significance of heat shock protein 47 in bleomycin-induced pulmonary fibrosis and explore the effect of NAC on the expression of HSP47 and collagen type I on the process of pulmonary fibrosis in rats.Methods 40 male healthy Sprague-Dawley rats were randomly divided into 5 experimental groups:the control group(group C),the bleomycin group(group M), the prednisone treatment group(group P), the NAC treatment group(group N), the NAC and prednisone treatment group (group P+N), each group contained 8 rats.The rat's model of pulmonary fibrosis was established by intratracheal instillation with BLM at a dose of 5mg-kg-1 except group C instead of the same dose normal saline (NS) solution.Group N received NAC before reproducing model a week and the other groups respectively received NS, prednisone, NAC or NAC and prednisone after reproducing model for 24 hours by gavage per day.All groups were killed on the 14th day after reproducing model.Calculating lung quotient and the right lungs were harvested for hemotoxylin-eosin staining and Masson staining to observe pulmonary fibrosis changes and determination of hydroxyproline content by alkali hydrolysis.The immunehistochemical method was used to detect the expressive levels of HSP47 and collagen type I in lungs.Results 1. The method that intratracheal instillation with bleomycin can be successfully reproduced the model of pulmonary fibrosis in rats.2. The comparison of lung quotient,content of Hyp and HE fibrosis scores among groups:group M was significantly higher than group C on the above all measures (P<0.01);Measures of group P,group N and group P+N were significantly lower than group M's(P<0.01). But group P,group N and group P+N were no statistically significant between each two groups (P>0.05) 3.The comparison of expression of HSP47 and collagen type I proteins detected by IHC among groups:group M was significantly higher than group C on the above two measures (P<0.01);GroupP,group N and group P+N were significantly lower than group M's (P<0.01).But group P,group N and group P+N were no statistically significant between each two groups (P> 0.05)Conclusions 1. HSP47 and collagen typeâ… were increased on pulmnary fibrosis and HSP47 may participate in the process of fibrosis in rats.2.NAC has antifibrogenic effect on the rat's model of pulmonary fibrosis and one of the mechanisms maybe achieved by dinimishing the content of collagen type I and hydroxyproline through inhibiting expression of HSP47. But the combination therapy of NAC and prednisone maynot had synergies effect on antifibrogenic fibrosis.