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目的探讨博莱霉素致大鼠肺间质纤维化肺组织前胶原Ⅰ和前胶原Ⅲ mRNA及蛋白质变化的意义。方法大鼠随机分为经气管内一次性灌注生理盐水为正常对照组,灌注博莱霉素分为博莱霉素3天组、7天组、14天组、30天组。分子杂交和免疫组化方法测定肺组织的前胶原Ⅰ,前胶原Ⅲ的mRNA和蛋白质表达。结果博莱霉素7天组前胶原Ⅰ、前胶原Ⅲ的mRNA高于正常对照组(P<0.01),14天组达到峰值水平,博莱霉素30天组的前胶原Ⅰ mRNA仍高于正常对照组(P<0.01),而前胶原Ⅲ的mRNA水平与正常对照组相接近(P<0.05)。免疫组化方法测定博莱霉素14天组、30天组肺组织Ⅰ型胶原蛋白表达高于正常对照组。结论博莱霉素致肺纤维化时,前胶原基因转录水平的升高,引起的胶原合成加速是肺间质胶原积聚的主要原因。“,”Objective Expression of procollagen Ⅰ (pro α 1(Ⅰ)) and Ⅲ (pro α 1(Ⅲ)) mRNA and collagen protein was measured in bleomycin treated mice to evaluate their roles in pulmonary fibrosis.Methods Male Wistar mice were divided into normal control group and groups treated by bleomycin on days 3,7,14,30.Each group included 5 mice,and mice were treated by single intratracheal instillation with sterile saline solution or with 5 mg/kg body weight of bleomycin.Mice were sacrificed at different days.Expression of pro α 1(Ⅰ) and pro α 1 (Ⅲ)mRNA was measured by dot blot and Northern blot hybridization.Expression of collagen protein was determined by immunohistochemical technique.Results The levels of pro α 1(Ⅰ) and pro α 1 (Ⅲ) mRNA in lungs of bleomycin group on day 7 were higher than those of control group(P<0.01),reaching a peak at day 14. After reaching the peak levels among two weeks, the levels of pro α 1(Ⅲ)mRNA in lungs of bleomycin group on day 30 declined slowly to approximately values of normal control group(P>0.05);but the levels of pro α 1(Ⅰ)mRNA on day 30 after bleomycin administration were higher than those of control group(P<0.01).The levels of protein expression of collagen Ⅰ in lungs of bleomycin group on days 14,30 were higher than those of control group(P<0.01).ConclusionrnThe results suggested that the metabolism of mRNAs for pro α 1(Ⅰ) and pro α 1 (Ⅲ) may be preferentially perturbed,and that the increase of collagen gene expression in the transcriptional level might be involved in the mechanism of collagen accumulation.