IL-6对人冠脉平滑肌细胞中PAPP-A、MMP-3、TIMP-1基因表达的影响

目的探讨细胞因子白介素6(IL-6)对人冠脉平滑肌细胞中妊娠相关血浆蛋白A(PAPP-A)、基质金属蛋白酶3(MMP-3)、金属蛋白酶组织抑制剂1(TIMP-1)基因表达的影响。方法应用10μg/L的IL-6刺激人冠脉平滑肌细胞,共同培养0,2,4,8,24,36h后收集细胞。应用不同浓度IL-6(0,5,10,50μg/L)刺激人冠脉平滑肌细胞,共同培养6h后收集细胞。应用实时定量PCR方法检测细胞内PAPP-A,MMP-3,TIMP-1基因表达量。结果在IL-6刺激下,PAPP-A、MMP-3表达量在2h时就开始发生上调,8h左右达高峰,而后开始下降;在不同浓度IL-6刺激下,PAPP-A,MMP-3表达量随着细胞因子浓度加大呈上升趋势。TIMP-1在IL-6刺激下,表达量在2h时就开始发生下调,4h左右达最低,而后开始上升;在不同浓度的IL-6刺激下,TIMP-1表达量随着细胞因子浓度加大呈下降趋势。结论炎性因子IL-6对冠脉平滑肌细胞中斑块稳定相关标记物PAPP-A、MMP-3、TIMP-1表达的影响,可能是炎症在急性冠脉综合征发生发展中作用机制之一。

The Influence of IL-6 on PAPP-A, MMP-3, TIMP-1 Gene Expression in Human Coronary Artery Smooth Muscle Cells

Objective To observe the effect of IL-6 on PAPP-A,MMP-3,TIMP-1 gene expression in human coronary artery smooth muscle cells. Methods Stimulate human coronary artery smooth muscle cells with IL-6 (10 ug/L),Isolate RNA and collect culture media after 0,2,4,8,24 and 36 h. Then stimulate human coronary artery smooth muscle cells with IL-6(0,5,10,50 ug/L),Isolate RNA and collect culture media after 6 h. Real-time PCR was performed on RNA to detect gene expression. Results In the same concentration of IL-6,PAPP-A and MMP-3 gene expression were up-regulation at 2 hour,at 8 hour the expression got to the peak ,then began to descent; In different concentration of IL-6,PAPP-A and MMP-3 gene expression were up-regulation with the dose of IL-6. In the same concentration of IL-6,TIMP-1 gene expression was down-regulation at 2 hour,at 4 hour the gene expression got to the lowest,then began to go up; In different concentration of IL-6,TIMP-1 gene expression was down-regulation with the dose of and IL-6. Conclusion It suggested that IL-6 can promote PAPP-A,MMP-3 gene expression and inhibit TIMP-1 gene expression in human coronary artery smooth muscle cells,and it may be one of the mechanisms of inflammation effect in acute coronary syndrome.