急性亚砷酸钠暴露对小鼠主动脉Nrf2通路的影响

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(P0.05);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(P0.05);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。

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

Objective To investigate the effect of acute sodium arserite 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 mRNA 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 mRNA level of GCLC significantly increased at 2 h with 5 mg/kg body weight sodium arsenic treatment and the mRNA levels of GCLM and NQO1 were statistically increased at 6 h (P＜0.05) with a dose-dependent manner.The Nrf2 mRNA levels in each group had no difference compared with the control group.The mRNA 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 mRNA 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 (P＜0.05).The Nrf2 mRNA levels in each group at 6 h had no significant difference compared with the control group.Compared with the control,the mRNA 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.