Oparil S, Chen S J, Chen Y F, Durand J N, Allen L, Thompson J A
Cardiovasc Res. 1999 Dec;44(3):608-14. doi: 10.1016/s0008-6363(99)00240-0.
This study tested, in ovariectomized rats, whether (1) adventitial activation plays a role in the vascular injury response, and (2) inhibition of adventitial activation and the subsequent wave of cell proliferation moving from adventitia to neointima contributes to the estrogen-induced attenuation of neointima formation in balloon injured carotid arteries.
Ovariectomized Sprague-Dawley rats were treated with either 17 beta-estradiol or vehicle beginning 72 h prior to balloon injury of the right common carotid artery and were sacrificed at 0, 3, 7, 14 and 28 days after injury. BrdU was administered 18 h and 12 h prior to sacrifice in order to quantitate mitotic activity in adventitia, media and neointima of the damaged vessel at specified times post injury.
Adventitial activation, evidenced by positive BrdU staining, was evident on the day of injury, peaked on day 3 and was resolved by day 7, thus preceding neointima formation. Numbers of BrdU labeled cells in adventitia on day 3 were significantly reduced in estrogen treated rats compared to controls. BrdU labeled cells were undetectable in media on the day of injury, appeared at day 3 and disappeared by day 14. Neointima appeared at day 7 and increased in area throughout the period of observation. Neointimal area and numbers of BrdU labeled cells in neointima were significantly reduced in estrogen treated rats compared to controls. These findings suggest that there is a wave of cell proliferation moving in an adventitia-to-lumen direction following endoluminal injury of the rat carotid artery and that estrogen modulates this proliferative response to injury.
These results support the hypothesis that adventitial activation contributes to the vascular injury response and that estrogen reduces this contribution.
本研究在去卵巢大鼠中测试，（1）外膜激活是否在血管损伤反应中起作用，以及（2）抑制外膜激活和随后从外膜向新生内膜移动的细胞增殖浪潮是否有助于雌激素诱导的球囊损伤颈动脉新生内膜形成的减弱。
去卵巢的Sprague-Dawley大鼠在右侧颈总动脉球囊损伤前72小时开始用17β-雌二醇或赋形剂治疗，并在损伤后0、3、7、14和28天处死。在处死前18小时和12小时给予BrdU，以定量损伤后特定时间受损血管外膜、中膜和新生内膜中的有丝分裂活性。
损伤当天可见BrdU阳性染色所证实的外膜激活，在第3天达到峰值，并在第7天消退，因此先于新生内膜形成。与对照组相比，雌激素治疗的大鼠在第3天外膜中BrdU标记细胞的数量显著减少。损伤当天中膜中未检测到BrdU标记细胞，在第3天出现并在第14天消失。新生内膜在第7天出现，并在整个观察期内面积增加。与对照组相比，雌激素治疗的大鼠新生内膜面积和新生内膜中BrdU标记细胞的数量显著减少。这些发现表明，大鼠颈动脉腔内损伤后有一波细胞增殖从外膜向管腔方向移动，并且雌激素调节这种对损伤的增殖反应。
这些结果支持以下假设，即外膜激活有助于血管损伤反应，而雌激素减少了这种作用。
