SiO_2对肺泡巨噬细胞基质金属蛋白酶-9/基质金属蛋白酶组织抑制因子-1和肺成纤维细胞Ⅲ型胶原表达的影响  

EFFECT OF SiO_2 ON THE EXPRESSION OF MMP-9,TIMP-1 IN HUMAN ALVEOLAR MACROPHAGES AND TYPE Ⅲ COLLAGEN IN HUMAN LUNG FIBROBLASTS

作　　者：朱兰[1] 冯莉[1] 伊雪[1] 王献华[1] 马小兵[1] 

机构地区：[1]河北联合大学基础医学院病理教研室,唐山063000

出　　处：《现代预防医学》2011年第14期2797-2800,共4页Modern Preventive Medicine

基　　金：河北省科学技术研究与发展计划项目(09276192D);河北省自然科学基金资助项目(C2008001007)

摘　　要：[目的]探讨SiO2能否通过肺泡巨噬细胞(AM)表达基质金属蛋白酶(MMPs)/基质金属蛋白酶机制因子(TIMPs)系统参与胶原的病理性累积。[方法]收集矽肺患者AM,分别用加入SiO2粉尘的培养液和无血清培养液培养2、6、12、18、24h,取出细胞爬片并吸出培养上清。将HELF分为处理组、对照组和空白对照组,于6h、12h、18h、24h、36h、48h取出细胞爬片、吸出上清。检测AM中MMP-9、TIMP-1及HELF条件培养上清中CⅢ的表达。[结果]经SiO2刺激的AM表达MMP-9增高,各点与同期对照组相比,差异有统计学意义(P﹤0.05或P﹤0.01);12、18、24hTIMP-1的表达与同期对照组相比也明显增高,差异有统计学意义(P﹤0.05或P﹤0.01),但表达较MMP-9晚且少,将处理组的MMP-9与同期的TIMP-1相比,MMP-9表达显著多于TIMP-1,差异有统计学意义(P﹤0.001);AM条件培养上清作用于HELF后,可使HELF上清中CⅢ明显升高,与同期对照组相比,差异有统计学意义(P﹤0.05或P﹤0.01)。[结论]SiO2可促使AM高表达MMP-9和TIMP-1,并通过AM的介导诱导HELF高表达CⅢ,AM通过表达MMPs/TIMPs系统在胶原的病理性累积中起到了重要作用。[Objective] To explore the effect of SiO2 on collagen pathologic deposition,and its effect mediated by human alveolar macrophage（AM）-expressed matrix metalloproteinase（MMP）,tissue inhibitor of metalloproteinase（TIMP）system or not.[Methods]AMs were collected from a silicotic patient by bronchoalveolar lavage and exposed to SiO2 or cultured in DMEM without serum respectively for 2,6,12,18 and 24h cultured human embryo lung fibroblast were allocated into a treated group,a control group,and a blank group.HELF was incubated with the cultured supernatant of AMs for 6,12,18,24,36 and 48h.Immunocytochemical and Western blot technology were used to detect MMP-9 and TIMP-1 expressions in AM and CⅢ expression in supernatant of HELF respectively.[Results]SiO2 stimulated expressions of MMP-9（at all time points）and TIMP-1（at 12,18,24h）in AM compared with control group（P﹤0.05 or P﹤0.01）.The expression of MMP-9 was remarkably more than that of TIMP-1 at all time points（P﹤0.001）.The expression of CⅢ in supernatant of HELF incubated with supernatant of AM exposed to SiO2 increased compared with control group（P﹤0.05 or P﹤0.01）.[Conclusion]SiO2 can stimulate expressions of MMP-9 and TIMP-1 in AM.Through AM mediation SiO2 can accelerate the expression of CⅢ.AM plays an important role in pathological accumulation of collagen through MMPs/TIMPs system.

关 键 词：二氧化硅 巨噬细胞 成纤维细胞 基质金属蛋白酶 胶原 

分 类 号：R563[医药卫生—呼吸系统]