睾酮对TNFα作用于内皮细胞表达HO1的影响.docVIP

睾酮对TNFα作用于内皮细胞表达HO1的影响 作者：井立省 张清华 蒋知新 高德路 李令华 柳杨 龙炫辉 【摘要】 目的 观察不同浓度睾酮对肿瘤坏死因子α(TNFα)作用于人脐静脉内皮细胞 (human umbilical vEin endothelial cells)ECV304表达血红素加氧酶1(HO1)的影响，初步探讨其作用机制。方法 用ELISA法观察不同浓度睾酮及雄激素受体拮抗剂Flutimide、雌激素受体拮抗剂ICI182，780对ECV304表达HO1干预作用。结果 睾酮在3×10-6,3×10-7,3×10-8,3×10-9mol/L几种浓度下均具有促进TNFα诱导的ECV304细胞表达HO1的量。与3.0×10-8mol/L睾酮干预组相比，予1.0×10-6mol/L ICI182，780预处理，ECV304细胞释放的HO1的量明显减少，并诱导HO1的表达呈时间(当t=24 h达到最理想的分泌量)、浓度依赖关系。结论 睾酮对TNFα诱导的ECV304细胞表达HO1的影响与其浓度有关，生理浓度睾酮对其具有一定的促进作用,而且这种生物学效应是部分通过转化为雌激素后，作用于雌激素受体实现。 【关键词】 睾酮;内皮细胞;血红素加氧酶1;肿瘤坏死因子α 　　【Abstract】 Objective To investigate the effects of testosterone of different concentrations on the process of tumor necrosis factorα(TNFα)influencing the releasing of hemeoxygenase1 (HO1) in human umbilical vEIn endothelial cells ECV304.Methods The effects of testosterone of different concentrations with or without its antagonist Flutamide or estrogen receptors antagonist ICI182, 780 on the senescence of ECV304 induced by TNFαwere studied by ELISA quality kit according to the manufacturer instructions strictly. Results Testosterone at low concentrations (3×10-9, 3×10-8 and 3×10-7 mol/L) had the trend of promoting the releasing of HO1 in ECV304 induced by TNFα, most obviously at the concentration of 3×10-8 mol/L(but P0.05 vs TNFαstimulated group), whereas higher concentration (3×10-6 mol/L) had stimulated effect on the senescence induced by TNFα (6.108±1.154, P0.05 vs TNFα). The estrogen receptors antagonist ICI182, 170 rather than Flutamide at concentration of 1×10-6mol/L inhibited the protection effect induced by testosterone at concentration of 3×10-8mol/L. Doseand time (with optimal secretion occurring at 24h)dependent effect of TNFαinduced the secretion of HO1. Conclusions Testosterone modulates the senescence of ECV304 induced by TNFαin a doserelated manner. And at physiological concentrations, testosterone has the trend of protecting it, mainly by transforming to estrogen acting on estrogen receptor.