巨噬细胞和MMP-9对肺成纤维细胞增生及合成Ⅳ型胶原的作用  

Effect of macrophage and matrix metalloproteinase-9 on proliferation of pulmonary fibroblast and synthesis of collagen Ⅳ

作　　者：宋良文[1] 孙丽[1] 刁瑞英[1] 李杨[1] 张勇[1] 尹纪业[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《中华放射医学与防护杂志》2006年第6期549-552,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金资助项目(30570545)

摘　　要：目的探讨放射性肺纤维化早期启动的发生机制。方法灌洗收集经^60Coγ射线照射后的Wistar大鼠肺泡巨噬细胞制备条件培养液，刺激培养的人肺成纤维细胞增生，用MTT法检测细胞增生活力，Western blot检测细胞合成Ⅳ型胶原含量的改变，酶谱分析检测细胞基质金属蛋白酶-9的活性。结果经条件培养液刺激后，人肺成纤维细胞的增殖活力明显增加，在48～72h之内作用明显HLF合成Ⅳ型胶原增多，12h达高峰，随后有所下降；12h后基质金属蛋白酶．9活性开始增高，于48h达高峰，72h开始下降。结论20Gy^60Coγ射线能刺激AM分泌某些细胞因子促进肺间质成纤维细胞增生及合成Ⅳ型胶原，与此同时后者能激活基质金属蛋白酶-9，降解增多的Co Ⅳ，参与肺损伤早期的重建过程。Objective To explore pathogenetic mechanism in initiation of radiation-induced pulmonary fibrosis. Methods Alveolar macrophages in Wistar rats irradiated by ^60Co γ-ray were collected by alveolar lavage; condition medium was prepared for stimulating human lung fibroblast （HLF） proliferation; HLF proliferation activity was determined by MTT method; collagen Ⅳ （Col Ⅳ ） in HLF was determined by Western blot; the activity of matrix metalloproteinase-9 （MMP-9） was determined by zymography. Results HLF proliferation activity was significantly increased after stimulation of condition medium, and the increase was most evident within 48-72 hs. Col Ⅳ synthesis in HLF was increased and reached a peak at 12 h after stimulation and then began to decrease. MMP-9 activity began to increase at 12 h and reached a peak at 48 h and then decreased after 72 h. Conclusions Cobalt-60 gamma ray irradiation of 20 Gy can stimulate secretion of some cytokines in alveolar macrophage to promote pulmonary interstitial fibroblast proliferation and synthesis of Col Ⅳ . Col Ⅳ can stimulate MMP-9 increase; MMP-9 can degrade excess Col Ⅳ . Such changes are involved in remodeling process of early pulmonary injury.

关 键 词：放射性肺损伤 肺泡巨噬细胞 成纤维细胞 Ⅳ型胶原 基质金属蛋白酶-9 

分 类 号：R363[医药卫生—病理学]