亚砷酸钠对血管增殖效应的体内体外研究

目的研究亚砷酸钠(NaAsO2)对血管的增殖效应,为地砷病的血管病变提供理论依据。方法应用鸡胚绒毛尿囊膜(CAM)血管新生模型研究亚砷酸钠体内对血管增生影响;以人脐静脉内皮细胞(HUV-EC)作为亚砷酸钠对血管增殖的体外研究模型,经Cell Counting Kit-8(CCK-8)测定HUV-EC细胞增殖;实时定量RT-PCR检测c-myc、c-jun mR-NAs表达水平。结果 NaAsO2对CAM有双向效应,低剂量NaAsO2促进血管增生,高剂量NaAsO2抑制血管增生;在一定浓度范围内,随NaAsO2浓度升高,对HUV-EC细胞增殖的抑制呈剂量-效应关系,明显降低c-myc、c-jun mRNA水平。结论亚砷酸钠可能通过下调c-myc、c-jun基因的表达来抑制HUV-EC增殖,可能是砷中毒引起血管疾病的发生机制之一。

in Vivo and in Vitro Studies on the Effect of Sodium Arsenite on the Angiogenesis

Objective The studies were carried out to explore the effect of sodium arsenite on the angiogenesis to provide theoretical explanation and practical measurement for arsenism.Methods The angiogenesis of Chorioallantoic membrane （CAM） were used as a model to evaluate in vivo effects of arsenic on it.The proliferation of human umbilical vein endothelial cells（HUV-EC） was used as an in vitro model to evaluate effects of arsenic on human vascular cells.Cell proliferation was assayed by CCK-8 kit.The mRNAs were analyzed by real time quantitative RT-PCR.Results Arsenic showed a bilateral effect on the angiogenesis in CAM model： the stimulating effect when exposed to low-level and suppressing effects when exposed to high-level arsenic.Sodium arsenite inhibited proliferation of HUV-EC in a dose-dependent manner when exposed to it in levels applied.Meanwhile,the mRNAs of c-jun and c-Myc were decreased following exposure to sodium arsenite.Conclusion and Discussion： Sodium arsenite inhibits proliferation of HUVEC through the down regulation of c-jun and c-Myc,suggesting they are the major signals for arsenic to exert its suppression on the proliferation of HUV-EC.