急性砷暴露对小鼠大脑皮层核因子Nrf2通路的影响  

Effects of acute arsenic exposure on Nrf2 pathway in mice cerebral cortex

作　　者：赵朔[1] 董丹丹[1] 段晓旭[1] 刘丹[1] 李冰[1] 

机构地区：[1]中国医科大学公共卫生学院劳动卫生教研室"砷生物学作用评价及砷中毒防治"辽宁省重点实验室,辽宁沈阳110001

出　　处：《环境与健康杂志》2013年第10期849-852,共4页Journal of Environment and Health

基　　金：国家自然科学基金(81172611)

摘　　要：目的探讨急性砷暴露小鼠大脑皮层核因子Nrf2(NF-E2-related factor 2)及其下游血红素单加氧酶-1(heme oxygenase-1,HO-1)、醌氧化还原酶[NAD(P)H:quinine oxidoreductase 1,NQO1]和谷胱甘肽-S-转移酶(glutathione-Stransferase,GST)mRNA和蛋白的表达。方法将48只健康8周龄清洁级昆明雌性小鼠按体重随机分为4组,即对照(生理盐水)组和5、10、20 mg/kg亚砷酸钠染毒组,每组12只。采用一次性灌胃方式进行染毒,染毒6 h后每组选择4只小鼠,检测大脑皮层中Nrf2、HO-1、NQO1、GST mRNA的表达水平;染毒24 h后每组选择5只小鼠,测定大脑皮层中丙二醛(malondialdehyde,MDA)含量,选择3只小鼠测定大脑皮层中Nrf2、HO-1、NQO1和GST蛋白的表达水平。结果与对照组比较,各剂量亚砷酸钠染毒组小鼠大脑皮层中MDA含量和大脑皮层核因子Nrf2及其下游HO-1、NQO1和GST mRNA和蛋白表达水平均升高。结论急性砷暴露可导致小鼠大脑皮层氧化损伤,并活化Nrf2信号通路。Objective To investigate the levels of the protein and mRNA expression of nuclear factor Nrf2 （NF-E2-related factor 2） and its downstream heine oxygenase-1 （HO-1）, NAD（P）H： quinine oxidoreductase 1 （NQO 1） and glutathione -S-transferase enzymes （GST） in mice cortex after acute arsenic exposure. Methods Healthy female Kunming mice were exposed to sodium arsenite by disposable gavage at doses of 0 mg/kg （control group）, 5 mg/kg, 10 mg/kg and 20 mg/kg, a total of 48 mice were randomly divided into four groups, 12 in each. 6 hours after treatment with NaAsO2, real time PCR was used to evaluate the mRNA levels of Nrf2, HO-1, NQO1 and GST genes. And 24 hours after treatment, the concentrations of malondialdehyde （MDA） in cortex were determined by thiobarbituric acid （TBA） method, and Western blot was used to evaluate the protein expression of Nrf2, HO-1, NQO1 and GST. Results The cortex levels of MDA in NaAsO2 exposure groups （5 mg/kg, 10 mg/kg and 20 mg/kg） were significantly higher compared with the control group （P〈0.05） with a dose-dependent manner. The protein and mRNA expressions of Nrf2, HO-1, NQO1 and GST were all up-regulated after arsenic exposure compared with the control respectively. Conclusion Acute arsenic exposure may cause oxidative damage and activate the Nif2-mediated signal pathway in mice cortex.

关 键 词：亚砷酸钠 Nrf2通路 大脑皮层 

分 类 号：R994.6[医药卫生—毒理学]