陈伟,欧阳劭,唐双阳,谭小武.肺纤维化鼠细胞凋亡及Fas/Bcl-2动态变化.[J].中南医学科学杂志.,2012,40(2):139-143.
肺纤维化鼠细胞凋亡及Fas/Bcl-2动态变化
The Expression of Fas/Bcl-2 and Apoptosis in the Epithelial Cells of Pulmonary Fibrosis Rats
投稿时间:2011-09-16  
DOI:
中文关键词:  肺纤维化  细胞凋亡  Fas  Bcl-2  大鼠
英文关键词:apoptosis  Fas  Bcl-2  pulmonary fibrosis
基金项目:湖南省教育厅科研项目(08C734)
作者单位
陈伟1,欧阳劭1,唐双阳2,谭小武1 1.南华大学附属第二医院呼吸内科湖南 衡阳 4210012.南华大学病原生物学研究所 
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中文摘要:
      目的探讨细胞凋亡及Fas/Bcl-2在肺纤维化发病中的作用。方法选取SD大鼠48只,随机分为对照组、模型组,每组各24只,应用博莱霉素(5 mg/kg)气管内注入建立实验性大鼠肺纤维化模型,对照组注入等量生理盐水,各组动物于7、14、28天随机处死8只,取肺组织采用HE染色观察病理变化,TUNEL法检测肺组织细胞凋亡、RT-PCR和免疫组织化学法分别检测肺组织Fas/Bcl-2 mRNA以及蛋白的表达。结果实验性大鼠肺纤维化发病过程中,呈现典型的肺泡炎(7天)、肺泡炎与纤维化并存(14天)及稳定的肺纤维化(28天)等表现;同时间段模型组肺组织细胞凋亡指数、Fas mRNA及蛋白表达均显著高于对照组(P<0.01)。Bcl-2 mRNA及蛋白表达显著低于对照组(P<0.01);模型组细胞凋亡从7天开始逐步升高,第28天达最高峰,Fas蛋白与Fas mRNA表达趋势与细胞凋亡相同;模型组Bcl-2蛋白与Bcl-2 mRNA表达在第7天开始下降,第14天达最低峰,第28天略有回升(P<0.05),但仍低于对照组(P<0.01)。结论肺泡及支气管上皮细胞凋亡与肺纤维化的形成有关,可能是肺纤维化的发病机制之一;Fas mRNA及蛋白表达上调和Bcl-2 mRNA及蛋白表达下调,可能引起肺上皮细胞的凋亡从而导致肺纤维化增生。
英文摘要:
      ObjectiveTo study the effect of apoptosis and Fas / Bcl-2 in the pathogenesis of pulmonary fibrosis.MethodsFouty-eight Sprague Dawley( SD )rats were randomly divided into two groups:normal control group(A group),model control group(B group).The model group were induced to produce pulmonary fibrosis with bleomycin endotracheally while the control group was given with normal saline instead in the same condition.Eight rats in model group were sacrificed on 7,14,and 28 days respectively after intratracheal instillation.Pathological changes in the lungs were evaluated by HE stain.The mRNA expression of Fas and Bcl-2 was evaluated by RT-PCR quantitative analysis,and the immunohistochemical method was used to investigate the change of Fas and Bcl-2 protein.TUNEL was used to detect the change of cell apoptosis.ResultsThe percentage of cell apoptosis detected by TUNEL in alveolar and bronachial epithelial cells of pulmonary fibrosis rats was higher than the normal control groups.The result of immunohistochemistry and RT-PCR suggested that the expression of Fas mRNA and Fas protein in model groups was higher than the normal control groups.The expression of Bcl-2 mRNA and Bcl-2 protein in model groups was lower than the normal control groups.The difference was significant(P<0.01).The result of immunohistochemistry and RT-PCR suggested that the expression of Fas protein and mRNA in alveolar and bronachial epithelial cells of pulmonary fibrosis rats also increased after 7 days by treating with bleomycin,increased on the 14th day and further increased on the 28th day;the expression of Bcl-2 protein and mRNA also decreased after 7 days by treating with bleomycin,reaches the trough on the 14th day.ConclusionsHigher expression of aoptosis in alveolar epithelial cells and Bronchial cells of pulmonary fibrosis rats can contribute to fibrogenesis;the apoptosis index of lung cells,Fas gene and protein up-regulated and Bcl-2 gene and protein down-regulated in lung tissue of pulmonary fibrosis,which may play an important role in the development of pulmonary fibrosis.
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