福辛普利及美托洛尔对涡流剪切应力诱导内皮细胞表达基质金属蛋白酶9影响的实验研究

Fosinopril but not metoprolol attenuated the increased matrix metalloproteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow

目的研究福辛普利、美托洛尔对涡流剪切应力诱导内皮细胞表达基质金属蛋白酶9(MMP9)的影响。方法将脐静脉内皮细胞分别放置于层流流室和涡流流室中,采用半定量逆转录聚合酶链反应(RT-PCR)及免疫印迹法(Westernblot)观察不同时间层流和涡流对脐静脉内皮细胞的影响,再将福辛普利及美托洛尔按1×10-7mol/L、1×10-5mol/L分别加入涡流流室培养液中,予以药物干预,观察MMP9表达变化。结果Westernblot及RT-PCR的检测结果均显示层流组内皮细胞未见MMP9的表达,涡流组培养4h可见MMP9的表达,24h后可见明显表达。涡流加福辛普利作用24h后可见MMP9的表达降低,涡流加美托洛尔干预24h后未见明显变化。结论福辛普利具有使涡流流动状态下内皮细胞表达MMP9的水平下调的作用。

Objective To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 （MMPg） expression of human umbilical vein endothelial cells （HUVECs） stimulated by oscillatory flow. Methods HUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations （ 1×10^-7mol/L、1×10^-5mol/L） of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively. Results MMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril （1×10^-7mol/L、1×10^-5mol/L, P 〈 0. 01, P 〈 0. 05, respectively） but not by co-incubation with metoprolol. Conclusion Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.