与蛋氨酸循环相关维生素对砷代谢及其所致氧化损伤影响的研究

Arsenic compounds are serious harm to human health. Skin damages, cardiovascular disease, diabetes and cancer may cause by chronic arsenic exposure. Arsenic was confirmed as human carcinogen by the international agency for research on cancer.Arsenic metabolism pattern is an important index of arsenic poisoning, our previous studies have shown that exogenous factors play a more important role in arsenic poisoning than environmental factors. Based on this, the focus of this research is folic acid and B vitamins which are important cofactors in methionine cycle. Methionine cycle can supply SAM and GSH as methyl donor and sulphur donor for arsenic metabolism. We choose mouse as the research object, establish high arsenic exposure and low folate levels animal model and then applying interference factors, explore the influence of folic acid and B vitamins to arsenic metabolism, oxidative damage caused by arsenic and methionine cycle of high arsenic exposure animal model. The research may also advance efforts to the study of arsenic metabolism and arsenic poisoning mechanism.

无机砷化物慢性暴露可造成包括神经、心血管、内分泌和呼吸系统在内的全身性损伤以及典型的皮肤损害，并引发多器官癌症，严重危害人类健康。砷代谢模式是反映砷中毒情况的重要指标，本课题组前期研究表明外源性环境因素对砷代谢模式的影响大于遗传因素。在此基础上，本研究以砷代谢过程中与甲基供体和巯基供体SAM和GSH生成密切相关的叶酸等B族维生素为重点，选取小鼠为研究对象，通过建立高砷暴露模型、低叶酸血症模型以及干预因素施加等方式，探讨叶酸等B族维生素对砷暴露个体砷代谢模式和氧化损伤指标的影响，并研究砷暴露及叶酸等B族维生素干预对蛋氨酸循环的影响。有望在砷代谢和砷中毒机制研究中取得新突破。

无机砷化物慢性暴露可造多脏器损害并引发癌症，严重危害人类健康。砷甲基化代谢与砷中毒关系密切。本研究以砷代谢过程中与甲基供体和巯基供体SAM和GSH生成密切相关蛋氨酸循环为重点，选取小鼠为研究对象，通过建立高砷暴露模型、低叶酸血症模型以及干预因素施加等方式，探讨叶酸等B族维生素对砷暴露个体砷代谢模式和氧化损伤指标的影响，并研究砷暴露及叶酸等B族维生素干预对蛋氨酸循环的影响。本研究通过建立砷暴露动物模型，采用砷含量测定，高效液相色谱，定量PCR 、蛋白印迹等技术研究砷暴露与蛋氨酸循环的关系。本研究取得的主要成果如下:.1. 高砷暴露会造成小鼠砷代谢能力减弱，氧化损伤加重，蛋氨酸代谢受阻;.2. 对高砷暴露小鼠给与叶酸和B6干预会增加砷在尿液中的排泄，拮抗砷所致氧化损伤和蛋氨酸代谢障碍;.3. 对砷暴露小鼠给与虾青素可以通过活化NF-кB并激活Nrf2信号通路拮抗砷所致的肝损伤。