Xing Dongqi, Miller Andrew, Novak Lea, Rocha Ricardo, Chen Yiu-Fai, Oparil Suzanne
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294, USA.
Circulation. 2004 Jan 20;109(2):234-41. doi: 10.1161/01.CIR.0000105700.95607.49. Epub 2003 Dec 29.
Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17beta-estradiol, E2) inhibits neointima formation in animal models, and the progestin medroxyprogesterone acetate (MPA) blocks this effect. This study tested the hypothesis that E2 inhibits the migration of inflammatory cells, particularly granulocytes, into the rat carotid arteries after acute endoluminal injury and that MPA blocks this effect.
Ovariectomized rats were randomly divided into subgroups and treated with E2, MPA, E2+MPA, or vehicle and subjected to balloon injury of the right carotid artery. After 1, 3, or 7 days, rats were euthanized, and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry. At 1 day, granulocytes (HIS48+ and CD45+), monocyte/macrophages (Mar1+ and CD45+), and T lymphocytes (CD3+ and CD45+) were increased 26-fold, 12-fold, and 3-fold, respectively, in injured compared with contralateral control arteries of vehicle-treated rats. Granulocytes and monocyte/macrophages decreased markedly by 3 days. E2 reduced the granulocyte and monocyte/macrophage populations of injured vessels by approximately 50% and increased T lymphocytes. MPA had no independent effect on inflammatory cells but completely blocked the effect of E2. Immunohistochemical examination verified these findings and localized inflammatory cells to the adventitial and periadventitial domains of injured vessels.
E2 may limit the neointimal response to endoluminal vascular injury, at least in part, by limiting leukocyte entry from adventitial/periadventitial tissues into injured vessels early in the injury response.
炎症在腔内血管损伤反应中起重要作用。雌激素（17β - 雌二醇，E2）在动物模型中可抑制新生内膜形成，而孕激素醋酸甲羟孕酮（MPA）可阻断此效应。本研究检验了以下假设：E2可抑制急性腔内损伤后炎症细胞，特别是粒细胞向大鼠颈动脉的迁移，且MPA可阻断此效应。
将去卵巢大鼠随机分为亚组，分别用E2、MPA、E2 + MPA或赋形剂处理，然后对右颈动脉进行球囊损伤。1、3或7天后，处死大鼠，通过流式细胞术分析颈动脉（损伤侧和对照侧）的炎症细胞。在第1天，与接受赋形剂处理大鼠的对侧对照动脉相比，损伤动脉中的粒细胞（HIS48 + 和CD45 +）、单核细胞/巨噬细胞（Mar1 + 和CD45 +）以及T淋巴细胞（CD3 + 和CD45 +）分别增加了26倍、12倍和3倍。粒细胞和单核细胞/巨噬细胞在3天时明显减少。E2使损伤血管中的粒细胞和单核细胞/巨噬细胞数量减少约50%，并增加了T淋巴细胞数量。MPA对炎症细胞无独立作用，但完全阻断了E2的作用。免疫组织化学检查证实了这些发现，并将炎症细胞定位在损伤血管的外膜和外膜周围区域。
E2可能至少部分地通过在损伤反应早期限制白细胞从外膜/外膜周围组织进入损伤血管，来限制对腔内血管损伤的新生内膜反应。
