三氧化二砷对小鼠肾氧化应激和甲硫氨酸亚砜还原酶基因表达的影响

Effect of arsenic trioxide treatment on oxidative stress and the expression of methionine sulfoxide reductases genes in mice kidney

砷暴露或过量吸收能导致多种疾病和病理损伤。本文旨在研究三氧化二砷(As_2O_3)暴露对小鼠肾氧化应激与甲硫氨酸亚砜还原酶基因表达的影响。对6周龄雄性小鼠分别用不同剂量(0、0.3、1.0、3.0、6.0、9.0 mg/kg)As_2O_3进行连续3周颈部皮下注射处理,然后分析小鼠肾脂质过氧化产物丙二醛(malondialdehyde,MDA)质量摩尔浓度、超氧化物歧化酶(superoxide dismutase,SOD)比活性和4种甲硫氨酸亚砜还原酶(methionine sulfoxide reductase,Msr)基因Msr A、Msr B1、Msr B2、Msr B3表达情况的变化。结果显示,不同剂量As_2O_3处理对小鼠肾膜脂过氧化水平没有显著影响;As_2O_3诱导了SOD比活性的增加,但9.0 mg/kg剂量组SOD比活性显著降低;不同Msr基因对As_2O_3表现出差异性反应,Msr A、Msr B3基因表达不受影响,As_2O_3处理后Msr B1基因的表达显著下调,而高剂量的As_2O_3则显著上调了Msr B2基因的表达。结果表明,9.0 mg/kg以下的As_2O_3暴露对小鼠肾膜脂过氧化影响不大,但明显诱导了SOD比活性的上升,Msr B2基因在小鼠肾适应As_2O_3暴露中发挥了重要作用。

Exposure or excessive absorption of arsenic can cause a variety of diseases and pathological damage. Experiments were carried out to investigate the effect of arsenic trioxide treatment on oxidative stress and the expression of methionine sulfoxide reductases genes in murine kidney.Six-week-old male mice were treated with different doses of As2O3（0, 0.3, 1.0, 3.0, 6.0, 9.0 mg/kg）, respectively. After 3 weeks, MDA content and SOD specific activity were measured in the kidney. The expression of Msr A,MsrB1,MsrB2,and MsrB3 genes were also analyzed by quantitative real-time PCR. No significant difference in MDA content was observed among mice kidney treated with different doses of As2O3.However, As2O3 treatment induced the increase of SOD activities in kidney, except 9.0 mg/kg As2O3. Furthermore, different Msr genes showed differential responses to As2O3 stress. The expression of Msr A and MsrB3 genes were not affected by As2O3 treatment. As2O3 treatment resulted in the down-regulation of Msr B1 expression while the expression of Msr B1 gene was up-regulated. It was suggested that As2O3 stress induced the increase of SOD activity and MsrB_2 gene played an important role in As2O3 stress in mice kidney.