急性亚砷酸钠暴露对小鼠主动脉Nrf2通路的影响  

Effects of acute sodium arsenite exposure on Nrf2 pathway in arota of mice

作　　者：吕航[1] 朱佳玉[1] 陈承杰[1] 孙汝[1] 王惠惠[1] 皮静波[1] 

机构地区：[1]中国医科大学公共卫生学院环境毒理学研究室,辽宁沈阳110122

出　　处：《环境与健康杂志》2017年第1期1-4,共4页Journal of Environment and Health

基　　金：国家自然科学基金(81502841;81573106)

摘　　要：目的研究急性亚砷酸钠暴露对小鼠主动脉NF-E2相关因子2(nuclear factor E2-related factor 2,Nrf2)通路的影响。方法选择健康成年清洁级雄性野生型C57BL/6小鼠作为实验动物。将15只小鼠按体重随机分成4组,分别为0(对照,n=3)及2、6、12h亚砷酸钠染毒组(n=4)。采用腹腔注射方式给予5 mg/kg亚砷酸钠溶液。将10只小鼠按体重随机分成3组,分别为对照(磷酸盐缓冲溶液,n=3)组和1.25 mg/kg(n=4)、5 mg/kg(n=3)亚砷酸钠染毒组。采用腹腔注射方式染毒6 h。检测小鼠主动脉中Nrf2及其下游基因谷氨酰半胱氨酸连接酶催化亚单位(GCLC)、谷氨酰半胱氨酸连接酶修饰亚单位(GCLM)以及NAD(P)H醌氧化还原酶(NQO1)m RNA的表达水平。结果与对照组相比,5 mg/kg亚砷酸钠染毒2 h小鼠主动脉GCLC m RNA的表达水平及染毒6 h小鼠主动脉GCLM、NQO1 m RNA的表达水平均较高,差异有统计学意义(P<0.05);而亚砷酸钠染毒不同时间小鼠主动脉Nrf2 m RNA的表达水平无明显变化。且随着亚砷酸钠染毒时间的延长,小鼠主动脉Nrf2、GCLC、GCLM及NQO1 m RNA的表达水平均呈先上升后下降的趋势。与对照组相比,5 mg/kg亚砷酸钠染毒6 h小鼠主动脉GCLC、GCLM及NQO1 m RNA的表达水平均较高,差异有统计学意义(P<0.05);而各剂量亚砷酸钠染毒6 h小鼠主动脉Nrf2 m RNA的表达水平均无明显改变。且随着亚砷酸钠染毒剂量的升高,小鼠主动脉Nrf2、GCLC、GCLM及NQO1 m RNA的表达水平均呈上升趋势。结论急性亚砷酸钠处理能激活小鼠主动脉Nrf2通路,提示急性无机砷暴露引起主动脉内发生氧化应激。Objective To investigate the effect of acute sodium arsenite exposure on nuclear factor E2-related factor 2（Nrf2）pathway in arota of mice. Methods Fifteen C57BL/6 male mice of clean grade were randomly divided into four groups by body weight, 0 h（control, n=3）, 2 h,6 h and 12 h（n=4） by intraperitoneal injection with sodium arsenite. The mice were randomly divided into three groups by body weight,control（PBS, n=3）,1.25 mg/kg body weight（n=4） and 5 mg/kg body weight（n=3）sodium arsenite treatment for 6 h by intraperitoneal injection. The m RNA levels of Nrf2 and Nrf2-regulated downstream genes such as GCLC, GCLM and NQO1 in arota were measured by real-time PCR. Results Compared with the control group,the m RNA level of GCLC significantly increased at 2 h with 5 mg/kg body weight sodium arsenic treatment and the m RNA levels of GCLM and NQO1 were statistically increased at 6 h（P0.05） with a dose-dependent manner. The Nrf2 m RNA levels in each group had no difference compared with the control group. The m RNA levels of Nrf2, GCLC, GCLM and NQO1 were significantly increased and then decreased as time went by with the treatment of sodium arsenite. Compared with the control,the m RNA levels of GCLC, GCLM and NQO1 with 5 mg/kg body weight sodium arsenite exposure were significantly higher than the other dose at 6 h（P0.05）. The Nrf2 m RNA levels in each group at 6 h had no significant difference compared with the control group. Compared with the control, the m RNA levels of GCLC, GCLM and NQO1 dose-dependently increased.Conclusion Acute arsenite exposure can activate mice arota Nrf2 signal pathway,which indicating sodium arsenite exposure can lead to arota oxidation damage.

关 键 词：NF-E2相关因子2 亚砷酸钠 主动脉 

分 类 号：R994.6[医药卫生—毒理学]