非诺贝特对LPC诱导脐静脉内皮细胞增殖、凋亡及eNOS基因表达的影响

Effects of fenofibrate on the proliferation and apoptosis and nitric oxide synthase expression of cultured human umbilical vein endothelial cells induced by lysophosphatidylcholine

目的:探讨非诺贝特对LPC诱导的脐静脉内皮细胞增殖、凋亡及内皮型一氧化氮合酶(eNOS)基因表达的影响。方法:体外培养人脐静脉内皮细胞(HUVECs),根据非诺贝特不同浓度分为正常对照组、LPC组、低浓度非诺贝特(10μmol/L)组、中浓度非诺贝特(50μmol/L)组、高浓度非诺贝特(100μmol/L)组,根据非诺贝特不同干预时间分为正常对照组、LPC组、非诺贝特(50μmol/L)干预6h组、12h组、24h组、48h组进行实验。分别观测不同浓度及不同时间非诺贝特内皮细胞增殖、凋亡、NO浓度及eNOS mRNA表达的变化。结果:与正常对照组比较,LPC抑制内皮细胞增殖,促进细胞凋亡,并使HUVECs eNOS mRNA表达降低,NO合成减少。非诺贝特可干预LPC对内皮细胞的作用,使内皮细胞增殖增强,细胞凋亡减少,eNOS mRNA表达升高,NO合成增加,且其作用呈时间-效应、浓度-效应依赖关系。结论:非诺贝特可改善LPC对HUVECs的影响,使内皮细胞增殖增强,凋亡减少,eNOSmRNA表达升高,NO合成增加,从而起到抗动脉硬化作用。

Objective To investigate the effects of fenofibrate on the proliferation and apoptosis and endothelial nitric oxide synthase （eNOS） mRNA expression of cultured human umbilical vein endothelial cells （HUVECs） induced by lysophosphatidylcholine （LPC）. Methods HUVECs were cultured in vitro. The study was designated to 5 groups according to fenofibrate concentration ： control group, LPC group, LPC ＋ low-concentration fenofibrate（ 10 μmol/L） , LPC ＋ middle-concentration fenofibrate（50 μmol/L） , and LPC ＋ high-concentration fenofibrate （100 μmol/L）. The study was designated to 6 groups according to the intervention time ： control group, LPC group, LPC ＋ fenofibrate （50 μmol/L）6 h, LPC ＋ fenofibrate 12 h, LPC ＋ fenofibrate 24 h, and LPC ＋ fenofibrate 48 h. The proliferation and apoptosis of HUVECs were evaluated by MTT assay, flow cytometry and fluorescence microscopy, respectively, eNOS mRNA were assayed by real time-PCR. Results Compared with the control group, LPC could inhibit the proliferation and induce apoptosis, and downregulate eNOS mRNA expression and decrease NO production of HUVECs. Fenofibrate could increase the proliferation and decrease the apoptosis, and up-regulate eNOS mRNA expression and enhance NO production in HUVECs. Conclusion Fenofibrate could improve the proliferation and inhibit the apoptosis, and up-regulate eNOS mRNA expression of HUVECs induced by LPC, which may be responsible for fenofibrate to prevent and treat atherosclerosis.