雌激素对血管内皮细胞一氧化氮合酶活性调控的受体机制研究

Study on mechanism of receptor-mediated modulation of nitric oxide synthase of vascular endothelial cell

目的 观察 17β 雌二醇对大鼠肺血管内皮细胞一氧化氮合酶 (NOS)活性的影响及雌激素受体在其中的作用。方法 用贴壁法和无酚红 16 40培养基培养大鼠肺血管内皮细胞 ,在不同浓度的 17β 雌二醇 (伴或不伴有雌激素受体拮抗剂代莫昔芬 )作用下 ,观察一定时间内内皮细胞的NOS活性及一氧化氮 (NO)的产量。放射配体结合分析技术检测内皮中的雌激素受体。结果 (1) 1～ 10nmol的 17β 雌二醇作用 8～ 2 4h ,内皮细胞的NO产量显著增加 (vs对照 P<0 .0 5 ) ,10nmol的 17β 雌二醇作用 8～ 2 4hNOS活性显著增强 (与对照比 ,8h ,P<0 .0 5 ;16h ,2 4h ,P<0 .0 1)。 (2 )大鼠肺血管内皮细胞中存在雌激素受体。 (3)雌激素受体拮抗剂他莫昔芬能显著抑制雌激素的上述作用 (P <0 .0 1)。结论 17β 雌二醇能增强大鼠血管内皮细胞的NOS活性和NO产量 ,该作用由雌激素受体介导 ,可能是雌激素降低血管阻力、抑制动脉粥样硬化作用的重要机理之一。

Objective To investigate the effect of 17β estradiol on vascular endothelial nitric oxide synthase (NOS).Methods Rat lung vascular endothelial cells(EC)were cultured according to the blocks explanting method and propagated in phenol red free 1640 medium.The cells were treated with several different concentrations of 17β estradiol (E 2 0.1 nmol-10 nmol) with or without estrogen receptor antagonist tamoxifen (1 nmol/L).The receptor binding assay (RBA) was adopted to measure the estrogen receptors in the endothelial cells.Results (1)Treatment with 17β estradiol for 8 hour to 24 hours significantly enhanced the production of NO (1 nmol/L,10 nmol/L E 2 vs control,P<0.05) and NOS activity (10 nmol E 2 vs control,8 h,P<0.05;16 h,24 h,P<0.01) in EC.(2) RBA showed the existence of estrogen receptors in endothelial cells.(3)Estrogen receptor antagonist tamoxifen significantly inhibited the effect of estradiol (P<0.01).Conclusion 17β estradiol could enhance the production of NO and the NOS activity in vascular endothelial cells via receptor mediated way,and estrogen receptor may be important in the release of NO from vascular endothelial cell.The result may contribute to explaining the beneficial effect of estrogen in the prevention of atherosclerosis.