不同雌激素水平对大鼠血管内皮细胞功能及血管内皮细胞粘附分子1表达的作用

目的研究雌激素对雌鼠肺血管内皮细胞功能及血管内皮细胞粘附分子-1(VCAM-1)表达的调节。方法（1）雌性SD大鼠24只分为假手术组、去势组、治疗组，采用放射免疫法检测血清中内皮素、前列环素的含量，铜-镉还原法测定血清中一氧化氮的产量。放射配体结合法检测肺血管内皮细胞中雌激素受体含量。（2）正常雌鼠肺培养的第2代血管内皮细胞，按不同浓度17-β雌二醇(17-βE2)分为A组（对照）、B组（3×10-8mol/L17-βE2）、C组（3×10-7mol/L17-βE2）；D组（3×10-6mol/L17-βE2）、E组（3×10-6mol/L17-βE2+3×10-6mol/L他莫西芬）处理48h，白细胞介素-1β作用后流式细胞仪分别检测各组VCAM-1表达量。结果(1)去势组雌鼠血中一氧化氮（18μmol/L±8μmol/L）、前列环素（8.5pg/ml±2.5pg/ml）均降低，治疗组二者水平明显升高（31μmol/L±7μmol/L，P<0.05；10.9pg/ml±3.4pg/ml），而内皮素含量变化则相反（170pg/ml±39pg/ml；100pg/ml±32pg/ml，P<0.05）。(2)去势组雌鼠血管内皮细胞中雌激素受体含量(fmol/106cell）显著降低（6.7±0.5)，治疗组雌激素受体含量维持在高水平（17.6±1.2，P<0.01）。(3)白细胞介素-1β作用后A组表达VCAM-1细胞百分率明显增高（17.5%±1.5%），B、C、D组表达VCAM-1细胞百分率显著降低（15.4%±1.42%、12.4%±0.34%、8.7%±0.27%，P<0.01）。结论雌激素水平可明显影响雌鼠血管内皮细胞内皮素、一氧化氮、前列环素的分泌，并可影响雌鼠血管内皮细胞中雌激素受体含量。雌二醇均可降低白细胞介素-1β诱发的雌鼠血管内皮细胞VCAM-1表达增高。

Effects of estrogen level on the function of vascular endothelial cells and expression of voscular cells adhesion molecule

OBJECTIVE: To observe the effect of estrogen level on the secreting function of vascular endothelial cells of female rats, and to study the regulation of content of estrogen receptor in VECs and the expression of vascular cells adhesion molecule-1 by estrogen level. METHODS: Radioimmunity was adopted to measure the content of endothelin and PGI2 in serum of female rats, and copper-niger reduction was chosen to measure the content of nitric oxide in serum. Radioligand binding and flow cytometry were used to measure the expression of estrogen receptor and vascular cells adhesion molecule-1 in female rat lung VECs respectively. RESULTS: (1) The content of nitric oxide (18 mumol/L +/- 8 mumol/L) and PGI2(8.5 pg/ml +/- 2.5 pg/ml) in blood decreased after castration and increased remarkably(31 mumol/L +/- 7 mumol/L, P < 0.05; 10.9 pg/ml +/- 3.4 pg/ml) after estrogen was supplemented. However, the content of endothelin changed conversely(170 pg/ml +/- 39 pg/ml, 100 pg/ml +/- 32 pg/ml, P < 0.05). (2) The content of ER in female rat lung VECs (6.7 +/- 0.5 fmol/10(6) cell) decreased remarkably after castration and increased after estrogen was supplemented(17.6 +/- 1.2 fmol/10(6) cell, P < 0.01). (3) The expression rate of VCAM-1 in VECs increased significantly after interleukin-1 beta acted on the cells(17.5% +/- 1.5%). 17-beta estradiol at the contents of 3 x 10(-8)-10(-6) mol/L all counteracted the increase in expression rate of VCAM-1 induced by interleukin-1 beta (15.4% +/- 1.42%, 12.4% +/- 0.34%, 8.7% +/- 0.27%, P < 0.01). CONCLUSION: The estrogen level influences the secreting of NO, PGI2 and ET of VECs, and influences the content of ER in VECs. 17-beta estradiol at 3 x 10(-8)-10(-6) mol/L counteracts the increase of VCAM-1 in VECs induced by interleukin-1 beta.