不同砷化合物对血管内皮细胞毒性的研究

Cytotoxicity study of vascular endothelial cells by different kinds of arsenicals

目的观察不同砷化合物对体外培养的牛主动脉血管内皮细胞（BAEC）的细胞毒性。方法培养的BAEC分别暴露于亚砷酸钠（NaAsO2，iAs^Ⅲ0～50μmol／L）、砷酸钠（Na2HAsO4，iAs^Ⅴ，0～10mmol／L）和甲基亚胂酸（CH3AsO，MMA^Ⅲ，0～2μmol／L）24h，应用四甲基偶氮唑盐（MTT）法测定细胞生存率；诱导性偶联质谱分光光度（ICP-MS）法测定细胞内总砷（tAs）含量。结果不同剂量范围内的iAs^Ⅲ、iAs^Ⅴ和MMA^Ⅲ均能够显著降低BAEC的细胞生存率（P〈0．01），且具有剂量．效应关系；iAs^Ⅲ、iAs^Ⅴ和MMA^Ⅲ暴露24h的BAEC细胞的50％生存率（IC50）经计算分别为24．1μmol／L、155．9μmol／L和1．7μmol／L，对BAEC的细胞毒性从大到小依次为：MMA^Ⅲ〉iAs^Ⅲ〉iAs^Ⅴ；相同暴露剂量和时间下，BAEC对MMA^Ⅲ暴露的砷摄取速度明显高于iAs^Ⅲ暴露（P〈0．01）。结论无机砷甲基化的活性中间产物MMA^Ⅲ对BAEC的细胞毒性要明显强于无机砷化合物。

Objective To observe the cytotoxicity of bovine aortic endothelial cells （BAEC） by different kinds of arsenicals. Methods Cultured BAEC was exposed to arsenite （iAs^Ⅲ , 0 - 50μmol/L）, arsenate （iAs^Ⅴ ,0 - 10mmol/L） or monomethylarsenous acid （MMA^Ⅲ ,0- 2μmol/L） for 24h, respectively. MTT assay and ICP-MS method were used to evaluate the cell viability and the total arsenic concentration （tAs） of BAEC, respectively. Results iAsm , iAsv and MMA^Ⅲ could all decrease the cell viability in a dose-dependent manner （P 〈 0.01 ）. The IC50 values for iAs^Ⅲ , iAsv and MMA^Ⅲ were determined to be approximately 24.1μmol/L, cytoxicity in BAEC was MMA^Ⅲ 〉 iAs^Ⅲ 〉 iAsv . The take-up 155.9μmol/L and 1.7μmol/L, respectively. The order of rate of MMA^Ⅲ by BAEC was significantly higher than iAsm exposure （ P 〈 0.01 ）. Conclusion MMA^Ⅲ , one of the active intermediate in inorganic arsenic methylation, is highly toxic in BAEC. Methylation of arsenic could be more like a bioactivation process rather than a detoxification process.