目的 探讨急性砷暴露小鼠脾脏核转录因子NF-E2相关因子2(NF-E2-related factor 2,Nrf2)及其下游血红素单加氧酶-1(HO-1)和谷胱甘肽-S-转移酶(GST)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,分别为对照(生理盐水)组和5、10、20 mg/kg亚砷酸钠染毒组,每组12只。给予小鼠一次性灌胃亚砷酸钠24 h后,测定脾组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力以及Nrf2、HO-1和GST蛋白的表达水平。结果 与对照组相比,各剂量亚砷酸钠染毒组小鼠脾组织中MDA含量均增加,差异有统计学意义(P〈0.05);20 mg/kg亚砷酸钠染毒组小鼠脾组织中SOD活力和10、20 mg/kg亚砷酸钠染毒组小鼠脾组织中GSH-Px活力均减少,差异有统计学意义(P〈0.05)。且随着亚砷酸钠染毒剂量的升高,小鼠脾组织中SOD和GSH-Px活力均呈下降趋势,而MDA含量呈上升趋势。与对照组相比,各剂量亚砷酸钠染毒组小鼠脾组织中HO-1和GSTO1/2蛋白的表达水平及10、20 mg/kg亚砷酸钠染毒组小鼠脾组织中Nrf2蛋白的表达水平均增加,差异有统计学意义(P〈0.05);且随着亚砷酸钠染毒剂量的升高,小鼠脾组织中Nrf2、HO-1和GSTO1/2蛋白的表达水平均呈上升趋势。结论 急性砷暴露在导致小鼠脾脏发生氧化损伤的同时,能够活化Nrf2信号通路,诱导下游抗氧化相关酶类蛋白表达,这可能是砷暴露刺激机体产生的一种防御应答反应。
Objective To investigate the protein expression of nuclear factor NF-E2-related factor 2 (Nrf2) and its downstream heine oxygenase-1 (HO-1) and glutathione-S-transferase (GST) in spleen of mice after actue arsenic exposure. Methods A total of 48 healthy Kunming mice (female, eight-week old) were randomly assigned to four groups by body weight (n=12), which were 0, 5, 10, 20 mg/kg sodium arsenite (NaAsO2), then MDA content,SOD activity and GSH-Px activity were determined, as well as the protein expression of Nrf2, HO-1 and GST were tested by Western blot 24 h after acute oral administration of NaAsO2. Results The MDA levels of each exposure group was significantly higher than the control group (P〈 0.05) with a dose-dependent relationship. However,the activity of SOD (20 mg/kg group) and GSH-Px (10 and 20 mg/kg group) were significantly decreased with a dose-dependent relationship (P〈0.05). Compared with the control, the proteins levels of Nrf2, HO-1 and GST all increased significantly and. dose-dependently in spleen tissues after acute arsenic exposure, respectively. Conclusion Acute arsenic exposure may induce obvious oxidative damage in the spleen of mice and activate the Nrf2 signal pathway, as well as the expression of its downstream enzymes HO-1 and GST.