白细胞介素-1β和肿瘤坏死因子-α对血管平滑肌细胞及基质金属蛋白酶-2骨桥蛋白基因表达的影响  

Effects of Interleukin-1β and Tumor Necrosis Factor-α on Matrix Metalloproteinase-2 and Osteopontin Gene Expression of Rat Vascular Smooth Muscle Cells

作　　者：周秀霞[1] 温进坤[1] 韩梅[1] 

机构地区：[1]河北医科大学基础医学研究所生物化学研究室,石家庄050017

出　　处：《中国动脉硬化杂志》1999年第4期292-293,共2页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金!(39770312);河北省自然科学基金!(398284)

摘　　要：促炎细胞因子白细胞介素－ １β和肿瘤坏死因子－ α是血管平滑肌细胞的强效促分裂原，为了探讨其促血管平滑肌细胞增殖是否与细胞外基质降解及粘附蛋白合成有关，本文以体外培养的血管平滑肌细胞为研究对象，应用Ｎｏｒｔｈｅｒｎ 印迹及基质金属蛋白酶－ ２ 活性酶图分析方法动态观察白细胞介素－ １β、肿瘤坏死因子－ α对血管平滑肌细胞表达基质金属蛋白酶－２ 及骨桥蛋白的影响。结果发现，白细胞介素－１β和肿瘤坏死因子－ α均可显著诱导基质金属蛋白酶－ ２ 及骨桥蛋白的基因表达，血管平滑肌细胞受两种细胞因子刺激１２ ｈ 后，基质金属蛋白酶－２ 及骨桥蛋白ｍＲＮＡ表达活性最高，分别达到对照细胞的３ 倍左右和１０ 倍以上。对细胞培养基基质金属蛋白酶活性进行酶图分析的结果发现，肿瘤坏死因子－α及白细胞介素－１β作用于血管平滑肌细胞１２ 及２４ ｈ 时，基质金属蛋白酶降解明胶的活性约为对照细胞培养基的２ 倍和１．５ 倍。提示这类细胞因子可同时在多位点上对血管平滑肌细胞的迁移与增殖发挥促进作用。Aim To explore whether or not the function of proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in promoting vascular smooth muscle cell (VSMC) proliferation was concerned with the degradation of extracellular matrix (ECM) and the synthesis of adhesion protein. Methods Cultured VSMCs were used as experimental objects, Northern blotting and zymography analysis were used to observe the effects of IL-1β and TNF-α on matrix metalloproteinase-2 (MMP-2) and osteopontin gene expression. Results Both IL-1β and TNF-α could obviously induce the gene expression of MMP-2 and osteopontin, which reached a peak at 12 h after treatment, and was about 3 times and over 10 times respectively, comparing with the control. The results of cell media MMP-2 zymography analysis showed that the activity of MMP-2 was about 2 times and 1.5 times, comparing with those from the control cell media. Conclusion IL-1β and TNF-α could simultaneously promote the migration and proliferation of VSMC by stimulating the gene expression of MMP-2 and osteopontin.

关 键 词：血管平滑肌细胞 IL-1Β 肿瘤坏死因子 MMP-2 

分 类 号：R543[医药卫生—心血管疾病]