洛伐他汀对兔血管平滑肌细胞转录因子活性的影响

Effect of lovastatin on rabbit vascular smooth muscle cells

目的 观察洛伐他汀对兔血管平滑肌细胞转录因子AP 1和NF κB结合活性及基质金属蛋白酶 9(MMP 9)表达的影响。方法 用 [γ 32 P] ATP标记寡聚核苷酸 ,采用电泳迁移率变动分析(EMSA)法测AP 1和NF κB结合活性 ,用酶谱分析法检测MMP 9表达水平。结果 洛伐他汀抑制血管平滑肌细胞MMP 9的生成且呈剂量 效应依赖关系 ,该抑制作用可被甲羟戊酸和焦磷酸二香叶酯而非角鲨烯所逆转 ;洛伐他汀减低AP 1和NF κB的结合活性。结论 洛伐他汀可抑制血管平滑肌细胞AP 1和NF κB结合活性 ,减少MMP 9的生成。

Objective To investigate the effect of lovastatin on binding activity of nuclear factor activator protein-1 (AP-1) to NF-κB and the expression of matrix metalloproteinase-9 (MMP-9) in rabbit vascular smooth muscle cells(VSMCs). Methods The oligonucleotide corresponding to the consensus NF-κB element or the consensus AP-1 element was labeled by [γ- 32P]-ATP. AP-1 and NF-κB binding activity was detected by electrophoretic mobility shift assay (EMSA), expression of MMP-9 was detected by zymography. Results Lovastatin inhibited the expression of MMP-9 in a dose-dependent manner, this effect was reversed by mevalonate and GGPP but not by squalene; lovastatin significantly decreased AP-1 and NF-κB binding activity. Conclusion Lovastatin decreased AP-1 and NF-κB binding activity and inhibited MMP-9 expression in rabbit VSMCs by the way of inhibiting prenylation of protein but not by cholestrol-lowering, and this might be the mechanism of its arteriosclerostic plaque stablizing effects.