亚砷酸钠对HUV-EC细胞凋亡，MMP，ROS及相关基因表达的影响

发布时间：2018-03-09 21:04

本文选题：亚砷酸钠　切入点：线粒体膜电位(MMP)　出处：《吉林大学》2008年硕士论文　论文类型：学位论文

【摘要】： 饮水型地砷病,是由于人们长期暴露于含砷量过高的生活饮用水而引起的一种生物地球化学性疾病。该病已成为严重威胁人类健康的一大公害病,日益受到各国政府和学术界的广泛关注和深入研究。但对其发病机制仍未能作出合理的解释,尚缺乏有效的防治措施,对砷暴露生物效应敏感标志物的研究也未取得突破性进展。为阐明砷对血管损伤的发生机制及发现新的砷敏感生物标志物,本研究利用人血管内皮HUV-EC细胞体外培养的实验模型,在较低水平剂量范围,系统研究了亚砷酸钠对细胞凋亡、活性氧化物ROS的产生及线粒体膜电位的作用,并对相关基因表达进行了分析,探讨其作用的分子机理。研究结果显示: 首次在人血管内皮细胞发现,亚砷酸钠在所研究的剂量范围即可引起线粒体膜电位的降低和细胞凋亡的增加,而且两者均与亚砷酸钠浓度呈明确的线性剂量-效应关系。细胞活性氧(ROS)含量则随亚砷酸钠剂量呈典型的双相剂量-效应关系,即在低水平亚砷酸钠作用下细胞内活性氧含量降低,而在较高剂量,细胞内活性氧含量随亚砷酸钠浓度的增加而增加。上述结果表明砷诱导的细胞凋亡,线粒体膜电位及细胞活性氧化物水平的改变在砷中毒早期血管损伤效应中起重要作用。本研究进一步证明了低水平亚砷酸钠显著地增加了SOD2和NQO1基因的表达量,表明这些氧化还原酶在降低细胞ROS含量,保护细胞免遭砷损伤中的重要作用;提示SOD2和NQO1基因表达水平的改变作为新的砷敏感生物标志物的潜在应用价值。
[Abstract]:Drinking water type arsenic disease is a biogeochemical disease caused by people's long-term exposure to drinking water containing too much arsenic. It has become a serious public hazard threatening human health. It has attracted increasing attention and in-depth research from governments and academia. However, its pathogenesis has not been properly explained and effective prevention and treatment measures are still lacking. In order to elucidate the mechanism of arsenic on vascular injury and discover new arsenic sensitive biomarkers, the experimental model of cultured human vascular endothelial HUV-EC cells in vitro was used in this study. In the lower dose range, the effects of sodium arsenite on cell apoptosis, production of active oxide ROS and mitochondrial membrane potential were systematically studied. The expression of related genes was analyzed, and the molecular mechanism of the action was discussed. It was first found in human vascular endothelial cells that sodium arsenite could induce the decrease of mitochondrial membrane potential and the increase of apoptosis in the studied dose range. Both of them showed a linear dose-effect relationship with the concentration of sodium arsenite, while the content of reactive oxygen species (Ros) in cells showed a typical biphasic dose-effect relationship with the dose of sodium arsenite. That is to say, the content of reactive oxygen in cells decreased under the action of low level sodium arsenite, but increased with the increase of concentration of sodium arsenite at a higher dose. These results indicate that arsenic induces apoptosis of cells. The changes of mitochondrial membrane potential and cellular active oxide level play an important role in the early vascular injury effect of arsenic poisoning. This study further demonstrated that low levels of sodium arsenite significantly increased the expression of SOD2 and NQO1 genes. These redox enzymes play an important role in reducing the content of ROS and protecting cells from arsenic injury, suggesting that the changes of SOD2 and NQO1 gene expression may be a potential biomarker for arsenic sensitivity.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R363

【相似文献】