Bakir S, Mori T, Durand J, Chen Y F, Thompson J A, Oparil S
The Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, USA.
Circulation. 2000 May 23;101(20):2342-4. doi: 10.1161/01.cir.101.20.2342.
Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the alpha or beta isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated.
Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg. kg(-1). d(-1), subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17beta estradiol (E2) (20 microgram. kg(-1). d(-1), S.C.) alone or combined with ICI 5 mg. kg(-1). d(-1), S.C.; with ICI 5 mg. kg(-1). d(-1) alone; or with vehicle according to a similar protocol. Two weeks after injury, rats were killed, and the carotid arteries were evaluated for neointima formation using morphometric analysis. ICI 182,780 blunted the E2-related protective effect and increased neointima formation in injured carotid arteries of intact female rats in a dose-dependent fashion. ICI had no effect on neointima formation in OVX, but addition of ICI to E2 in OVX blocked the inhibitory effect of exogenous E2 on neointima formation.
These results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.
先前的研究表明，雌激素（E2）在多种血管损伤动物模型中具有血管保护作用，包括雌激素受体（ER）基因α或β亚型同源性破坏的小鼠，这使得血管保护作用的ER依赖性受到质疑。本研究使用非选择性ER拮抗剂ICI 182,780来检验E2在大鼠颈动脉损伤模型中的血管保护作用是由ER介导的这一假设。
将完整的雌性Sprague-Dawley大鼠分为4组，在右侧颈总动脉球囊损伤前开始，皮下注射非选择性ER拮抗剂ICI 182,780（ICI；0.5、1.5或5 mg·kg⁻¹·d⁻¹）或赋形剂，并持续14天。四组去卵巢大鼠（OVX）分别单独接受17β-雌二醇（E2）（20 μg·kg⁻¹·d⁻¹，皮下注射）或与5 mg·kg⁻¹·d⁻¹的ICI联合使用；单独使用5 mg·kg⁻¹·d⁻¹的ICI；或按照类似方案使用赋形剂。损伤后两周，处死大鼠，使用形态计量分析评估颈动脉内膜增生情况。ICI 182,780以剂量依赖性方式减弱了完整雌性大鼠损伤颈动脉中E2相关的保护作用，并增加了内膜增生。ICI对OVX的内膜增生无影响，但在OVX中将ICI添加到E2中可阻断外源性E2对内膜增生的抑制作用。
这些结果表明，E2在球囊损伤的大鼠颈动脉模型中的血管保护作用是由ER介导的。
