李新春,宋良文,杨蕾蕾,等.吡啡尼酮对抗放射所致肺成纤维细胞转化的作用研究[J].中华放射医学与防护杂志,2010,30(2):156-160.LI Xin-chun,SONG Liang-wen,YANG Lei-lei,et al.Effects of pirfenidone antagonizing pulmonary fibroblasts transformation caused by radiation[J].Chin J Radiol Med Prot,2010,30(2):156-160
吡啡尼酮对抗放射所致肺成纤维细胞转化的作用研究
Effects of pirfenidone antagonizing pulmonary fibroblasts transformation caused by radiation
投稿时间:2009-01-19  
DOI:
中文关键词:  吡啡尼酮  放射性肺损伤  成纤维细胞  转化
英文关键词:Pirfenidone  Radiational pulmonary injury  Fibroblasts  Transformation
基金项目:国家自然科学基金(30570545)
作者单位E-mail
李新春 100850 北京,军事医学科学院放射与辐射医学研究所  
宋良文 100850 北京,军事医学科学院放射与辐射医学研究所 Lsong1@yahoo.com.cn 
杨蕾蕾 100850 北京,军事医学科学院放射与辐射医学研究所  
王少霞 100850 北京,军事医学科学院放射与辐射医学研究所  
刁瑞英 100850 北京,军事医学科学院放射与辐射医学研究所  
王晓民 100850 北京,军事医学科学院放射与辐射医学研究所  
徐新萍 100850 北京,军事医学科学院放射与辐射医学研究所  
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中文摘要:
      目的 探讨放射性肺损伤过程中吡啡尼酮对抗肺成纤维细胞(Fb)向肌成纤维细胞(MFb)转化的作用。方法 将Wistar大鼠随机分为正常对照组、单纯照射组和照射+给药组,照射前2 d开始灌胃给予吡啡尼酮,用20 Gy60Co γ射线进行全胸照射,于照射后2周应用图像分析测定肺组织放射性炎性反应范围的面密度;计算肺组织湿/干重比;免疫组化检测肺组织成纤维细胞α-平滑肌肌动蛋白(α-SMA)表达。应用免疫细胞化学和四甲基偶氮唑盐(MTT)比色法分别检测人肺成纤维细胞(HLF)表达TGF-β1和细胞异常增生的程度。结果 和单纯照射组相比,照射+给药组大鼠肺组织炎性病变区面密度、湿/干重比和α-SMA含量较照射组分别减少14.0%、3.82%和 52.8%。吡啡尼酮可抑制照射促进HLF表达TGF-β1和细胞增生的作用,且此种抑制作用和给药剂量呈明显的依赖关系。 结论 吡啡尼酮对放射性肺损伤早期的间质性肺炎具有明显的对抗作用,并且可显著抑制肺Fb异常增生、TGF-β1表达和向肌成纤维细胞方向转化,有利于放射性肺纤维化的有效防治。
英文摘要:
      Objective To explore the effects of pirfenidone antagonizing pulmonary fibroblasts (Fb) transformation towards myofibroblasts (MFb) during the course of radiational pulmonary injury. Methods Wistar rats were randomly assigned into three groups: normal control group, radiation group and radiation and administration group.The rats were given with pirfenidone by intragastric administration 2 days before radiation. The whole breasts of rats were irradiated by 60Co γ-rays at a dose of 20 Gy and 2 weeks after radiation area density of pulmonary radiational inflammation was determined by image analysis. The ratio of pulmonary humid weight and dry weight was calculated. α-smooth muscle actin (α-SMA) expression of pulmonary fibroblasts was examined by immunohistochemistry. Human lung fibroblasts (HLF) abnormal proliferation and TGF-β1 expression were respectively detected by MTT colorimetric method and immunocytochemical stain. Results Compared with radiation group, the area density of pulmonary inflammatory pathological changes, the ratio of pulmonary humid weight and dry weight and pulmonary α-SMA content in rats of radiation and administration group were reduced by 14.0%, 3.82% and 52.8%, respectively. Pirfenidone could suppress radiation-enhanced HLF proliferation and TGF-β1 expression in a dose-dependent manner. Conclusions Pirfenidone can antagonize the induction of interstitial pneumonia in the earlier period of radiational pulmonary injury evidently, and it can significantly suppress HLF abnormal proliferation, TGF-β1 expression and transformation towards MFb, which help for preventing and curing radiational pulmonary fibrosis effectively.
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