溴氰菊酯对大鼠脑组织自由基生成和转录因子Nrf2表达的影响

Effect of deltamethrin on production of free radical and transcription factor Nrf2 in rats＇ brain tissue

目的研究溴氰菊酯（DM）诱导大鼠脑组织中自由基生成和对转录因子Nrf2的影响。方法（1）8只大鼠随机分成4组，即橄榄油对照组、DM染毒组、叔丁基对苯二酚（tBHQ）组和tBHQ＋DM组。在预先喂饲雄性大鼠tBHQ3d后，用12．50mg／kg DM染毒大鼠5d，用电子自旋共振（ESR）直接法测定海马组织中的自由基。（2）18只雄性大鼠分为3组，分别给予橄榄油及3．13、12．50mg／kg DM连续染毒5d，用Western blot方法测定大脑皮层和海马细胞质或细胞核中Nrf2蛋白水平。结果（1）DM染毒组大鼠与tBHQ＋DM组大鼠海马中自由基水平增高，分别是对照组的2．45倍和2．97倍，差异有统计学意义（P〈0．05）。（2）低、高剂量DM染毒大鼠大脑皮层的细胞质中Nrf2蛋白表达水平增高，分别是对照组的1．68倍和1．34倍；细胞核中的Nrf2蛋白表达呈剂量-效应关系性增高，分别是对照组的1．51倍和2．29倍，差异有统计学意义（P〈0．05或P〈0．01）。（3）低、高剂量DM染毒大鼠海马组织的细胞质Nrf2蛋白表达呈剂量-效应关系性增高，分别是对照组的2．26倍和3．58倍；细胞核中的Nrf2蛋白表达也增高，分别是对照组的2．42倍和2．45倍，差异有统计学意义（P〈0．05）。结论DM染毒能诱导大鼠海马组织中自由基生成，DM能诱导大脑皮层和海马组织中的Nrf2蛋白表达。

Objective To explore the effect of deltamethrin （DM） on production of free radical and transcription factor Nrf2 in rats＇ brain tissue. Methods 8 male rats were randomly assigned to four groups and administered with 1% W/W tertiary butylhydroquinone （tBHQ） or olive oil for 3 days, prior to exposure to DM and then with 12.50 mg or 0rag DM/Kg BW for 5 days. The level of free radical in rats＇ hippocampus tissue was detected by electron spin resonance （ESR） spectroscopy. 18 male rats were randomly assigned to three groups and administered with i.p. （daily dose was respectively 0, 3.13, 12.50 mg/kg DM） for five days. After treatment, Nrf2 protein levels in the cytoplasmic and nuclear fractions of both cerebral cortex and hippocampus tissue were measured by western blot. Results The level of free radical in hippoeampus tissue of rats administered by DM and pretreatment with tBHQ prior to DM were increased to a 2.45- fold and 2.97- fold of values of control group, respectively （P〈0.05）. Nrf2 protein levels in the cytoplasmic fractions of cerebral cortex of both low and high dose group were significantly increased, 1.68- fold and 1.34- fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of cerebral cortex of both low and high dose group were increased in a dose- dependent model, 1.51- fold and 2.29- fold of values of control group, respectively （P〈 0.01 ）. Nrf2 protein levels in the cytoplasmic fractions of hippocampus tissue of both low and high dose group were increased in a dose- dependent model, 2.26- fold and 3.58- fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of hippocampus tissue of both low and high dose group were increased, 2.42- fold and 2,45- fold of values of control group, respectively （P〈0.01）. Conclusion The studies in vivo demonstrate that DM treatment could induce free radical production and expression of Nrf2 protein in both cerebral cortex and hippocampus tissue and activate Nrf2.