一氧化氮在17-β雌二醇抑制血管平滑肌细胞增殖和原癌基因c-fos表达中的作用

杨丹, 谈智,   刘培庆, 潘敬运, 王庭槐*
(中山医科大学生理学教研室，广州  510080)

摘 要:

实验利用大鼠血管平滑肌细胞(vascular smooth muscle cells, VSMC)作为模型，观察17-β雌二醇(E2)对VSMC增殖和原癌基因c-fos表达的影响，并探讨VSMC源性一氧化氮(NO)在其中的作用。检测指标包括NO释放的测定、 细胞计数、 3H-Tdr掺入、 噻唑蓝(MTT)测定和c-fos mRNA表达。结果显示，E2(10-12~10－８ mol/L)呈浓度依赖性地促进VSMC中NO的释放；10－８ mol/L E2 能明显抑制10％小牛血清(FCS)和10－７ mol/L 内皮素-1(ET-1)诱导的细胞增殖和DNA合成，E2的抑制作用均可被雌激素受体 (ER) 拮抗剂tamoxifen (10－７  mol/L)和一氧化氮合酶抑制剂L-NAME(10－６ mol/L)明显减轻；E2(10－８ mol/L)可明显抑制10－７ mol/L ET-1诱导的VSMC c-fos表达，这种抑制作用可被L-NAME  (10－６ mol/L) 明显减轻。这些结果提示E2能抑制VSMC增殖和原癌基因c-fos表达，这和促进VSMC的NO释放密切相关，而且该作用至少部分通过ER介导。

关键词: 
血管平滑肌细胞; 雌激素; 一氧化氮; 一氧化氮合酶; c-fos
学科分类号:  Q463; R331.36

17β-estradiol inhibits vascular smooth muscle cell   proliferation and c-fos expression: role of  nitric oxide

YANG Dan, TAN Zhi, LIU Pei-Qing,   PAN Jing-Yun, WANG Ting-Huai*
(Department of physiology, Sun Yat-sen University of Medical Sciences, Guangzhou 510080)
　

Abstract: 
Rat vascular smooth muscle cells (VSMC) were used to study the effect of 17β-estradiol (E2) on cellular proliferation (cell counting),  DNA synthesis (3H thymidine incorporation) ,  MTT,  c-fos mRNA expression and nitric oxide (NO) release. The results obtained showed that   E2(10－12～10－８ mol/L) induced NO release from VSMC in a concentration-dependent manner; 10－８  mol/L E2 significantly inhibited VSMC cellular proliferation and DNA synthesis induced by 10% FCS and 10－７ mol/L ET-1, which was obviously reversed by 10－７ mol/L tamoxifen and 10－６ mol/L L-NAME; after a pretreatment  for 24 hours,  10－８ mol/L E2 significantly inhibited VSMC c-fos mRNA expression induced by 10－７ mol/L ET-1,  which was also obviously reversed by 10－６ mol/L L-NAME .  These results suggest that the inhibitory effects of E2 on VSMC cellular proliferation and c-fos mRNA expression are closely related with NO release in VSMC,  which is,  at least,    partly medicated by ER .
　

Key words:
 vascular smooth muscle cell;  estrogen; nitric oxide;  nitric oxide synthase;  c-fos

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