17β-雌二醇对人脐静脉内皮细胞内皮型一氧化氮合酶和一氧化氮的影响

17β-Estradiol-induced Changes of Endothelial Nitric Oxide Synthase and Nitric Oxide in Human Umbilical Vein Endothelial Cells

背景:门静脉高压时门静脉系统血管内皮广泛受损,除压力增高、血流冲击等因素外,体液因子的变化也是重要损伤因素之一。目的:研究雌激素对人脐静脉内皮细胞(HUVEC)内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)的影响,探讨其在门静脉高压血管内皮病变中的意义。方法:以不同浓度17β-雌二醇和雌激素受体拮抗剂他莫昔芬单独或联合作用于体外培养的HUVEC,检测eNOS活性和NO含量变化。结果:与对照组相比,1×10^(-9)～1×10^(-7)mol/L 17β-雌二醇均可增加HUVEC eNOS活性,提高NO含量;1×10^(-8)～1×10^(-6)mol/L他莫昔芬对HUVEC eNOS活性和NO含量均无明显影响:1×10^(-7)mol/L 17β-雌二醇对经1×10^(-6)mol/L他莫昔芬预处理的HUVEC eNOS活性和NO含量无明显影响。结论:17β-雌二醇可显著增加HUVEC eNOS活性,提高NO含量,他莫昔芬则可阻断其作用。门静脉高压血管内皮病变的形成与雌激素的作用有一定关系。

Background： The vascular endothelium of portal venous system is seriously damaged during portal hypertension. Change of humoral factors is the important damaging factor besides the increase of pressure and impact of blood flow. Aims： To investigate the changes of endothelial nitric oxide synthase （eNOS） and nitric oxide （NO） induced by estrogen in human umbilical vein endothelial cells （HUVEC）, and to explore the influence of estrogen on vascular endothelial lesions in portal hypertension. Methods： The cultured HUVEC were treated with 17β-estradiol and tamoxifen, an antagonist of estrogen receptor at different concentrations. The activity of eNOS and concentration of NO in HUVEC were measured. Results： 1×10^-9-1×10^-7 mol/L 17β-estradiol up-regulated the eNOS activity and NO concentration in HUVEC as compared with those in the control group, whereas 1×10^-8-1×10^-6 mol/L tamoxifen and 1×10^-7 mol/L 17β-estradiol combined with 1×10^-6 mol/L tamoxifen had no such effect. Conclusions： 17β-estradiol significantly promotes the activity of eNOS and the concentration of NO in HUVEC, and tamoxifen can block the effect of 17β-estradiol on HUVEC. The vascular endothelial lesions in portal hypertension might be concerned with the effect of estrogen.