ESTROGEN INHIBITS THE RESPONSE-TO-INJURY IN A MOUSE CAROTID-ARTERY MODEL
ESTROGEN INHIBITS THE RESPONSE-TO-INJURY IN A MOUSE CAROTID-ARTERY MODEL
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DOI：
10.1172/jci118307
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发表时间：
1995-11-01
影响因子：
15.9
通讯作者：
MENDELSOHN, ME
中科院分区：
文献类型：
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作者：
SULLIVAN, TR;KARAS, RH;MENDELSOHN, ME
雌激素的动脉粥样硬化保护作用是有据可查的，但这些作用的机制还不清楚。为了研究生理（纳摩尔）雌激素水平对动脉损伤反应的作用，我们将小鼠颈动脉损伤模型应用于卵巢切除的C57 BL/6 J小鼠。用载体处理小鼠（-E2，n = 10）或17 β-雌二醇（+E2，n = 10），7 d后对侧颈动脉损伤，将来自-E2和+E2动物的（正常= NL）和损伤的颈动脉压力固定，收获，并通过定量形态测定法分析，在第0、7和14天，+E2小鼠中的E2水平始终在纳摩尔范围内（2.1-2.5 nM）。14 d时，-E2组内膜和中膜面积均显著增加（-E2 vs NL，P均< 0.05），而+E2组与正常水平相比无变化（+E2 vs NL，P = NS和+E2 vs -E2，P均< 0.05）。通过溴脱氧尿苷（BrdU）标记评估，在-E2小鼠中，细胞增殖显著高于NL，但在雌激素替代组中，这种增殖显著减弱（总BrdU阳性细胞/切片：NL = 6.4+/-4.5 -E2 = 113+/-26，+E2 = 40+/-3.7; -E2 vs NL，P < 0.05; +E2 vs NL，P = NS; -E2 vs +E2，P < 0.05）。这些数据（a）表明生理水平的雌激素替代显著抑制小鼠颈动脉对损伤的反应;（B）支持该模型在研究雌激素对血管损伤反应的生物学效应中的实用性;和（c）表明雌激素对损伤血管中血管平滑肌细胞增殖的直接影响。
The atheroprotective effects of estrogen are well documented, but the mechanisms responsible for these effects are not well understood. To study the role of physiologic (nanomolar) estrogen levels on the arterial response-to-injury, we applied a mouse carotid artery injury model to ovariectomized C57BL/6J mice. Mice were treated with vehicle (-E2, n = 10) or 17 beta-estradiol (+E2, n = 10) for 7 d, subjected to unilateral carotid injury, and 14 d later contralateral (normal = NL) and injured carotids from -E2 and +E2 animals were pressure fixed, harvested, and analyzed by quantitative morphometry, E2 levels in +E2 mice were consistently in the nanomolar range (2.1-2.5 nM) at days 0, 7, and 14. At 14 d, measures of both intimal and medial area were markedly increased in the -E2 group: (-E2 vs NL, P < 0.05 for both), but were unchanged from normal levels in the +E2 group (+E2 vs NL, P = NS and +E2 vs -E2, P < 0.05 for both). Cellular proliferation, as assessed by bromodeoxyuridine (BrdU) labeling, was significantly increased over NL in the -E2 mice, but this increase was markedly attenuated in the estrogen replacement group (total BrdU positive cells/section: NL = 6.4+/-4.5 -E2 = 113+/-26, +E2 = 40+/-3.7; -E2 vs NL, P < 0.05; +E2 vs NL, P = NS; -E2 vs +E2, P < 0.05). These data (a) demonstrate significant suppression of the mouse carotid response-to-injury by physiologic levels of estrogen replacement; (b) support the utility of this model in the study of the biologic effects of estrogen on the vascular-injury response; and (c) suggest a direct effect of estrogen on vascular smooth muscle cell proliferation in injured vessels.