Levine R L, Chen S J, Durand J, Chen Y F, Oparil S
University of Alabama at Birmingham, Vascular Biology and Hypertension Program, USA.
Circulation. 1996 Nov 1;94(9):2221-7. doi: 10.1161/01.cir.94.9.2221.
Estrogen blunts the neointimal proliferative response to balloon injury of the carotid artery in intact female rats and gonadectomized rats of both sexes. This study tested whether, in gonadectomized rats of both sexes. (1) progestin (medroxyprogesterone acetate, MPA) alters neointima formation in injured carotid arteries, (2) addition of MPA alters the antiproliferative effects of estrogen, and (3) an interaction between MPA and estrogen can be accounted for by MPA-induced alterations in serum 17 beta-estradiol levels.
Male and female Sprague-Dawley rats were subjected to gonadectomy, then were randomly divided into four subgroups and treated with either (1) 17 beta-estradiol, (2) MPA, (3) 17 beta-estradiol + MPA, or (4) vehicle, and balloon injury of the right common carotid artery was carried out. Two weeks later, rats were killed by overdose of pentobarbital, and the carotid arteries were subjected to morphometric analysis for evaluation of myointimal thickening. Estradiol inhibited myointimal proliferation after vascular injury in gonadectomized rats of both sexes (P < .05). MPA alone did not alter neointima formation, but addition of MPA to estradiol completely blocked the antiproliferative effects of estrogen without altering serum 17 beta-estradiol levels.
These data indicate that exogenous progestin given alone does not alter the vascular injury response in the rat carotid injury model but that addition of a progestin blocks the antiproliferative effects of estrogen in this model. These effects are seen in gonadectomized rats of both sexes. These findings have direct implications for postmenopausal hormone replacement therapy in humans.
雌激素可抑制完整雌性大鼠和两性去势大鼠颈动脉球囊损伤后的内膜增生反应。本研究旨在检测在两性去势大鼠中：（1）孕激素（醋酸甲羟孕酮，MPA）是否会改变损伤颈动脉的内膜形成；（2）添加MPA是否会改变雌激素的抗增殖作用；（3）MPA与雌激素之间的相互作用是否可由MPA诱导的血清17β-雌二醇水平变化来解释。
将雄性和雌性Sprague-Dawley大鼠去势，然后随机分为四个亚组，分别用以下药物处理：（1）17β-雌二醇；（2）MPA；（3）17β-雌二醇+MPA；（4）赋形剂，随后对右侧颈总动脉进行球囊损伤。两周后，过量戊巴比妥钠处死大鼠，对颈动脉进行形态计量分析以评估肌内膜增厚情况。雌二醇可抑制两性去势大鼠血管损伤后的肌内膜增殖（P<0.05）。单独使用MPA不会改变内膜形成，但在雌二醇中添加MPA可完全阻断雌激素的抗增殖作用，且不改变血清17β-雌二醇水平。
这些数据表明，单独给予外源性孕激素不会改变大鼠颈动脉损伤模型中的血管损伤反应，但在该模型中添加孕激素可阻断雌激素的抗增殖作用。在两性去势大鼠中均观察到了这些效应。这些发现对人类绝经后激素替代疗法具有直接意义。
