国际呼吸杂志
國際呼吸雜誌
국제호흡잡지
INTERNATIONAL JOURNAL OF RESPIRATION
2012年
14期
1058-1061,封3
,共5页
陈伟%何振华%欧阳劭%谭小武
陳偉%何振華%歐暘劭%譚小武
진위%하진화%구양소%담소무
肺纤维化%细胞凋亡%Bid%Bcl-xl%大鼠
肺纖維化%細胞凋亡%Bid%Bcl-xl%大鼠
폐섬유화%세포조망%Bid%Bcl-xl%대서
Pulmonary fibrosis%Apoptosis%Bid%Bcl-xl%Rat
目的 探讨肺纤维化大鼠中Bcl-2家族部分蛋白介导的线粒体途径引起上皮细胞凋亡的动态变化及相关关系.方法 选取SD大鼠48只,随机分为4组:空白对照组(24只)、模型7d组(8只)、模型14 d组(8只)、模型28 d组(8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,空白对照组注入等量生理盐水,各组动物于第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和免疫组化法分别检测肺组织Bid、Bcl-xl 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 d)、肺泡炎与纤维化并存(14 d)及稳定的肺纤维化(28 d)等表现；同时间段模型组肺组织细胞凋亡指数、Bid mRNA及蛋白表达均显著高于空白对照组(P＜0.01),Bcl- xl mRNA及蛋白表达显著低于空白对照组(P＜0.01);模型组细胞凋亡与Bid蛋白及mRNA从第7天开始逐步升高,第28天达最高峰,Bid mRNA与细胞凋亡指数呈正相关(r=0.8275,t =7.937 5,P＜0.01)；模型组Bcl-xl蛋白与Bcl-xl mRNA表达在第7天开始下降,第28天达最低峰,Bcl-xl mRNA与细胞凋亡指数呈负相关(r=-0.633 8,t=-4.489,P＜0.01); Bcl-xl mRNA与Bid mRNA无明显相关性(r=-0.3869,t=-2.2986,P＞0.05).结论 细胞凋亡在肺纤维形成中起重要作用,肺纤维化细胞凋亡可能与Bcl-2家族蛋白的表达失衡有关.
目的 探討肺纖維化大鼠中Bcl-2傢族部分蛋白介導的線粒體途徑引起上皮細胞凋亡的動態變化及相關關繫.方法 選取SD大鼠48隻,隨機分為4組:空白對照組(24隻)、模型7d組(8隻)、模型14 d組(8隻)、模型28 d組(8隻).應用博萊黴素(5 mg/kg)氣管內註入建立實驗性大鼠肺纖維化模型,空白對照組註入等量生理鹽水,各組動物于第7、14、28天隨機處死8隻,取肺組織採用HE染色觀察病理變化,TUNEL法檢測肺組織細胞凋亡,RT-PCR和免疫組化法分彆檢測肺組織Bid、Bcl-xl mRNA以及蛋白的錶達.結果 實驗性大鼠肺纖維化髮病過程中,呈現典型的肺泡炎(7 d)、肺泡炎與纖維化併存(14 d)及穩定的肺纖維化(28 d)等錶現；同時間段模型組肺組織細胞凋亡指數、Bid mRNA及蛋白錶達均顯著高于空白對照組(P＜0.01),Bcl- xl mRNA及蛋白錶達顯著低于空白對照組(P＜0.01);模型組細胞凋亡與Bid蛋白及mRNA從第7天開始逐步升高,第28天達最高峰,Bid mRNA與細胞凋亡指數呈正相關(r=0.8275,t =7.937 5,P＜0.01)；模型組Bcl-xl蛋白與Bcl-xl mRNA錶達在第7天開始下降,第28天達最低峰,Bcl-xl mRNA與細胞凋亡指數呈負相關(r=-0.633 8,t=-4.489,P＜0.01); Bcl-xl mRNA與Bid mRNA無明顯相關性(r=-0.3869,t=-2.2986,P＞0.05).結論 細胞凋亡在肺纖維形成中起重要作用,肺纖維化細胞凋亡可能與Bcl-2傢族蛋白的錶達失衡有關.
목적 탐토폐섬유화대서중Bcl-2가족부분단백개도적선립체도경인기상피세포조망적동태변화급상관관계.방법 선취SD대서48지,수궤분위4조:공백대조조(24지)、모형7d조(8지)、모형14 d조(8지)、모형28 d조(8지).응용박래매소(5 mg/kg)기관내주입건립실험성대서폐섬유화모형,공백대조조주입등량생리염수,각조동물우제7、14、28천수궤처사8지,취폐조직채용HE염색관찰병리변화,TUNEL법검측폐조직세포조망,RT-PCR화면역조화법분별검측폐조직Bid、Bcl-xl mRNA이급단백적표체.결과 실험성대서폐섬유화발병과정중,정현전형적폐포염(7 d)、폐포염여섬유화병존(14 d)급은정적폐섬유화(28 d)등표현；동시간단모형조폐조직세포조망지수、Bid mRNA급단백표체균현저고우공백대조조(P＜0.01),Bcl- xl mRNA급단백표체현저저우공백대조조(P＜0.01);모형조세포조망여Bid단백급mRNA종제7천개시축보승고,제28천체최고봉,Bid mRNA여세포조망지수정정상관(r=0.8275,t =7.937 5,P＜0.01)；모형조Bcl-xl단백여Bcl-xl mRNA표체재제7천개시하강,제28천체최저봉,Bcl-xl mRNA여세포조망지수정부상관(r=-0.633 8,t=-4.489,P＜0.01); Bcl-xl mRNA여Bid mRNA무명현상관성(r=-0.3869,t=-2.2986,P＞0.05).결론 세포조망재폐섬유형성중기중요작용,폐섬유화세포조망가능여Bcl-2가족단백적표체실형유관.
Objective To investigate the expressions of Bcl-2 family,which leads to apoptotic cell of the pulmonary fibrosis rats.Methods Fouty-eight Sprague-Dawley (SD) rats were randomly divided into four groups:control group,model group 7 d,14 d,28 d.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 each 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 expressions of Bid and Bcl-xl were evaluated by RT-PCR quantitative analysis,and the immunohistochemical method was used to investigate the change of Bid and Bcl-xl protein.TUNEL was used to detect the change of cell apoptosis.Results The percentage of cell apoptosis in alveolar and bronachial epithelial cells of pulmonary fibrosis rats was higher than that in normal control group.The result of immunohistochemistry and RT-PCR suggested that the expressions of Bid mRNA and Bid protein in model groups were higher than those in normal control group.The expressions of Bcl-xl mRNA and Bcl-xl protein in model groups were lower than those in normal control group ( P ＜ 0.01).The.expressions of Bid protein and mRNA also increased after 7 d by treated with bleomycin,increased on the 14th day and further increased on the 28th day.The expression of Bcl-xl protein and mRNA also decreased after 7 d by treated with bleomycin,reaches the trough in the 28th day.There was significant correlation between TUNEL results and the expression of Bid/Bcl-xl mRNA.Conclusions Higher expression of apoptosis in alveolar epithelial cells and bronchial cells of pulmonary fibrosis rats can contribute to fibrogenesis.The apoptosis index of lung cells may be related to the expression imbalance of Bcl-2 family protein.
