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诱导型一氧化氮合酶在17#beta#-雌二醇诱导的血管平滑肌细胞周期阻滞中的作用

杨丹, 付晓东, 李永勇, 谈智, 王庭槐, 潘敬运

中山大学中山医学院生理教研室.广东,广州 510089

摘要

E_(2)明显增加iNOS的活性和蛋白表达,在30min和12h时能诱导VSMC的iNOS活性明显增加,而60min和24h时VSMC的iNOS活性与对照组无显著差异,不呈明显浓度依赖性,雌激素受体(ER)拮抗剂Tamoxifen和L-NAME能明显抑制E_(2)诱导的VSMC iNOS活性增加;E_(2)增加VSMC的iNOS蛋白表达的作用在3h时起效,12h达高峰,以后逐渐下降,呈浓度依赖性,Tamoxifen能明显抑制E_(2)诱导的VSMC iNOS蛋白表达;E_(2)明显抑制ET-1诱导的S期细胞百分比和G_(2)+S/G_(1)增加,使VSMC在G_(1)期发生细胞周期阻滞,这些作用可被预先给予L-NAME所明显减轻。上述结果提示,E_(2)使ET-1刺激的VSMC细胞周期循环在G_(1)期发生阻滞与增加VSMC iNOS活性有关,该作用至少部分通过ER介导。

关键词： 血管平滑肌; 雌激素; 一氧化氮; 一氧化氮合酶; 细胞周期

Role of inducible nitric oxide synthase in the vascular smooth muscle cells cycle arrest induced by 17#beta#-estradiol

Yang Dan, Fu Xiaodong, Li Yongyong, Tan Zhi, Wang Tinghuai, Pan Jingyun

Department of Physiology,Sun Yat-sen University,Zhongshan Medical College.Guangzhou 510089,Guangdong

Abstract

30min and 12h. These effects were significantly inhibited by estrogen receptor (ER) antagonist Tamoxifen (0.1 #mu#mol/L) and NOS inhibitor L-NAME (1 #mu#mol/L). E_(2) increased iNOS protein expression of VSMCs in a dose-dependent manner. The effect of E_(2) on iNOS protein expression of VSMCs started at 3 h, distinctly increased at 12 h and then decreased. Tamoxifen significantly inhibited the E_(2)-induced iNOS protein expression of VSMCs. ET-1 increased cell percentage of S phase and G_(2)+S/G_(1). This effect was inhibited by E_(2). L-NAME significantly attenuated the inhibitory effect of E_(2) on cell cycle of VSMCs. The results suggest that E_(2) induced G_(1) arrest of VSMCs, which was associated with an increase in iNOS activity and protein expression of VSMCs. These effects were at least mediated by estrogen receptor partly.

Key words: Vascular smooth muscle;Estrogen;Nnitric oxide;nitric oxide synthase;Cell cycle

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引用本文：

杨丹, 付晓东, 李永勇, 谈智, 王庭槐, 潘敬运. 诱导型一氧化氮合酶在17#beta#-雌二醇诱导的血管平滑肌细胞周期阻滞中的作用[J]. 生理学报 2003; 55 (6): .

Yang Dan, Fu Xiaodong, Li Yongyong, Tan Zhi, Wang Tinghuai, Pan Jingyun. Role of inducible nitric oxide synthase in the vascular smooth muscle cells cycle arrest induced by 17#beta#-estradiol. Acta Physiol Sin 2003; 55 (6): (in Chinese with English abstract).