• 关键词：亚硝酸钠  镉  人肝癌SMMC-7721细胞  毒物兴奋效应  预适应

• 基金项目：国家重大环保公益项目专项(No200809115);省部共建河南大学科研项目(NoSBGJ090702)

• 史齐
• 河南大学医学院 环境医学研究所, 开封 475004

• 李延红
• 河南大学医学院 环境医学研究所, 开封 475004

• 皇甫超申
• 1. 河南大学医学院 环境医学研究所, 开封 475004; 2. 河南大学环境与健康工程中心, 开封 475004

• 石贞玉
• 河南大学医学院 环境医学研究所, 开封 475004

• 厉永强
• 河南大学医学院 环境医学研究所, 开封 475004

• 刘彬
• 河南大学医学院 环境医学研究所, 开封 475004

• 摘要：为了研究亚硝酸钠对肝源性细胞的毒物兴奋效应和拮抗镉诱导的细胞凋亡作用,以人体肝癌细胞SMMC-7721为模型,用3.13～3200mg·L^-1亚硝酸钠作用24h,并采用四甲基偶氮唑蓝(MTT)法检测细胞的增殖活性.结果表明,细胞增殖活性表现出毒物兴奋效应.在毒物兴奋效应浓度范围内,选取最小效应浓度的亚硝酸钠(17mg·L^-1)预适应细胞24h,然后再用25μmol·L^-1氯化镉处理12h,细胞增殖活性结果表明,预适应的细胞能够耐受镉损害,这种细胞保护作用可以被一氧化氮清除剂抑制.流式细胞术及Hoechst 33258/PI荧光双染结果表明,亚硝酸钠预适应的细胞能够耐受镉诱导的细胞凋亡.亚硝酸钠预适应的细胞再用氯化镉处理,与单纯氯化镉处理组相比,细胞内丙二醛(MDA)含量下降,超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性升高.同时,免疫细胞化学结果也显示,金属硫蛋白(MT)表达升高.总体而言,亚硝酸钠在3.13～800mg·L^-1浓度范围内可促进细胞增殖活性并能够耐受镉诱导的细胞凋亡.

• Abstract：We investigated the proliferation hormesis and antagonism induced by sodium nitrite against cadmium-induced apoptosis in human liver-derived cells SMMC-7721.The cells were treated with a series of concentrations of NaNO₂ for 24 hours and their viability was measured by thiazolyl blue tetrazolium bromide (MTT).NaNO₂ pretreatment of SMMC-7721 cells at concentrations ranging from 3.13 mg·L^-1 to 3200 mg·L^-1 showed a hormetic effect.Aminimal preconditioning dose was chosen in the hormetic zone (17 mg·L^-1).Pretreatment of SMMC-7721 cells with the minimal dose for 24 hours had a cytoprotective effect against the deleterious effects of 12 hours exposure to 25μmol·L^-1 of cadmium chloride (CdCl₂),but the cytoprotective effect was inhibited by the nitric oxide scavenger c-PTIO.Fluorescence activated cell sorting (FACS) and morphology analysis showed that pretreatment with 17 mg·L^-1 of NaNO₂ for 24 hours also inhibited CdCl₂-induced apoptosis.In comparison with a single CdCl₂ challenge,cells pretreated with NaNO₂ followed by CdCl₂ challenge showed significantly decreased levels of malondialdehyde (MDA),elevated levels of metallothionein (MT) as well as increased superoxide dismutase (SOD) and catalase (CAT) activities.The results demonstrated that low doses of NaNO₂ could enhance the proliferation viability and toleration of CdCl₂-induced cell apoptosis in SMMC-7721.

• Key words：sodium nitrite  cadmium  human hepatoma SMMC-7721 cells  hormesis  preconditioning

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