Sex difference in urocortin production is contributory to the gender disparity in a rat model of vasculitis induced by sodium laurate.
Sex difference in urocortin production is contributory to the gender disparity in a rat model of vasculitis induced by sodium laurate.
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DOI：
10.1210/en.2013-1572
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发表时间：
2013-09
期刊：
影响因子：
4.8
通讯作者：
Rong Wan;Lai Jin;Chao Zhu;Yunxin Liu;Li Li-Li;Rui Guo;Shengnan Li
中科院分区：
文献类型：
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作者：
Rong Wan;Lai Jin;Chao Zhu;Yunxin Liu;Li Li-Li;Rui Guo;Shengnan Li
心血管疾病是最常见的导致死亡的疾病，在同一年龄段，男性多于女性。越来越多的证据表明，尿皮质素（Ucn 1），自分泌或旁分泌的促炎因子，可以通过性激素的调节。本研究的目的是调查Ucn 1在月桂酸钠诱导的血管炎模型中的性别差异中的作用。注射月桂酸钠后第14天，大鼠出现明显的血管炎体征。通过组织学检查观察大鼠股动脉的炎症状态。观察到显著的性别差异，男性的症状比女性严重得多。在男性中，血清Ucn 1、前列腺素雌二醇和可溶性细胞间粘附分子-1水平以及股动脉中Ucn 1、环氧合酶-2和细胞间粘附分子-1的表达均高于女性。睾丸切除术显著改善了血管炎的症状，同时降低了血浆Ucn 1水平。然而，雌二醇补充后，睾丸切除术未能改善炎症状态进一步。在女性中，卵巢切除术和/或双氢睾酮的补充显着增加UCN 1水平和血管炎的症状加重。此外，ip给药兔抗血清Ucn 1几乎消除了血管炎的性别差异。这些结果表明，该模型的血管炎是雄激素反应性的，通过手术切除睾丸的激素操作可以大大减轻血管炎的症状。此外，Ucn 1是血管炎性别差异的一个促成因素，二氢睾酮促进Ucn 1分泌加剧了血管炎的发展。
Cardiovascular diseases, the most common leading death diseases, occur more in men than women of the same ages. Increasing evidence shows that urocortin (Ucn1), an autocrine or paracrine pro-inflammatory factor, can be regulated by sex hormones. The purpose of the study is to investigate the role of Ucn1 in gender disparity in a sodium laurate-induced vasculitis model. Rats exhibited visible signs of vasculitis on the 14th day after sodium laurate injection. Inflammatory states of the rat femoral artery were observed by histological examination. Significant gender disparity, with the symptoms much grosser in males than females, was seen. In males, the serum levels of Ucn1, prostaglandin estradiol, and soluble intercellular adhesion molecule-1 and the expressions of Ucn1, cyclooxygenase-2, and intercellular adhesion molecule-1 in femoral artery were higher than those in females. Orchidectomy significantly ameliorated the symptoms of vasculitis accompanied with a decrease in the plasma Ucn1 level. However, estradiol supplement after orchidectomy failed to improve the inflammatory states further. In females, ovariectomy and/or dihydrotestosterone supplement significantly increased Ucn1 level and exacerbated symptoms of vasculitis. Furthermore, ip administration of rabbit antiserum to Ucn1 almost abolished the gender differences in vasculitis. These results demonstrated that vasculitis of this model is androgen-responsive and hormonal manipulation by surgical orchidectomy could substantially attenuate the symptoms of vasculitis. Moreover, Ucn1 is a contributory factor to the gender disparity in vasculitis and dihydrotestosterone-promoted Ucn1 secretion exacerbated the development of vasculitis.