李明,宋良文,刁瑞英,王少霞,徐新萍,罗庆良.巨噬细胞金属蛋白酶-12在放射性肺损伤早期组织重建中的作用[J].中华放射医学与防护杂志,2008,28(5):479-483
巨噬细胞金属蛋白酶-12在放射性肺损伤早期组织重建中的作用
Role of MMP-12 on tissue remodeling at early stage of radiation_induced pulmonary injury
投稿时间:2008-05-08  
DOI:
中文关键词:  金属蛋白酶-12  放射性肺损伤  弹力纤维  信息交流  组织重建
英文关键词:Macrophage metalloproteinase-12  Radiation pulmonary injury  Elastin  Cross talking  Tissue remodeling
基金项目:
作者单位E-mail
李明 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 
刁瑞英 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  
徐新萍 100850 北京, 军事医学科学院放射与辐射医学研究所  
罗庆良 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 探讨巨噬细胞金属蛋白酶(MMP-12)在放射性肺损伤早期肺组织重建中的作用。方法 用20 Gy 60Co γ射线对Wistar大鼠进行全胸照射,分别于照后1、2和4周进行肺组织取材,RT-PCR方法检测MMP-12基因表达,酶谱分析法检测MMP-2、MMP-9和MMP-12酶活性,组织特殊染色法检测弹力纤维降解,电镜观察Ⅱ型细胞与肺泡隔间质细胞间的"信息交流(cross talking)"现象,ELISA检测肺泡灌洗液中TGF-β1和TNF-α含量,免疫组化检测肺组织α-平滑肌肌动蛋白(α-SMA)表达。结果 照射后1、2和4周肺组织MMP-12基因表达增加,2~4周MMP-12酶活性增高;照射后1周肺泡基底膜弹力纤维出现降解断裂,4周时最为严重;电镜观察发现肺泡Ⅱ型细胞与间质细胞间发生Cross talking现象,肺泡灌洗液TGF-β1和TNF-α含量与α-SMA免疫组化阳性信号皆随照射后时间延长而增高。结论 照射后肺组织MMP-12表达增加,可能通过降解基底膜弹力纤维启动肺组织重建,导致肺损伤朝着纤维化方向发展。
英文摘要:
      Objective To explore the role of MMP-12 on tissue remodeling at early stage of radiation_induced pulmonary injury. Methods Wistar rats irradiated by 60Co γ-rays to the whole lungs were sacrificed at 1, 2, 4 weeks. MMP-12 mRNA expression was detected by RT-PCR. MMP-2, MMP-9, MMP-12 activities were determined by zymography.The degradation and collapse of elastin were determined by tissue elastin particular staining; the "cross talking" phenomenon between alveolar typeⅡ cells and mesenchymal cells was observed under electron microscope; the expression of TGF-β1 and TNF-α in BALF was detected by ELISA. The expression of α-SMA was determined by immunohistochemistry. Results The mRNA expression of MMP-12 displayed a significant elevation at 1, 2, 4 weeks after irradiation. MMP-12 activity increased at 2, 4 weeks after irradiation. Elastin began to degrade and collapse at 1 week, which became worst 4 weeks after irradiation. The cross talking phenomenon was found under electron microscope. The expression of TGF-β1, TNF-α and α-SMA was increased gradually as time elapse after irradiation. Conclusions 60Co γ-ray irradiation can promote pulmonary MMP-12 expression, initiate pulmonary tissue remodeling by degradation of elastin, and make the pulmonary injury develop towards pulmonary fibrosis eventually.
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