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目的研究甲基汞(methylmereury,MeHg)致大鼠脑皮质的氧化损伤,并探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对甲基汞致大鼠脑皮质氧化损伤的拮抗作用。方法将32只清洁级健康Wistar大鼠按体重随机分为4组,分别为对照(生理盐水)组、低剂量(4μmol/kg)MeHg组、高剂量(12μmol/kg)MeHg组和NAC(1 mmol/kg)预处理+MeHg(12μmol/kg)组,每组8只,雌雄各半。NAC预处理+MeHg组皮下注射NAC溶液,对照组和低、高剂量MeHg组均皮下注射生理盐水;注射2h后,采用腹腔注射方式染毒MeHg,连续染毒4周,测定脑组织蛋白质巯基、羰基和丙二醛(MDA)、8-羟基脱氧鸟苷(8-OHdG)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、三磷酸腺苷(ATP)酶的活力。结果 MeHg染毒大鼠脑皮质中MDA、蛋白质羰基、8-OHdG的含量升高(P<0.05),蛋白质巯基的含量降低和SOD、GSH-Px、ATP酶的活力降低(P<0.05);与高剂量MeHg组比较,NAC预处理+MeHg组大鼠脑皮质中上述指标均得到显著改善(P<0.05)。结论 MeHg可导致大鼠脑皮质的氧化损伤;NAC对甲基汞所致大鼠脑皮质氧化损伤有一定的拮抗作用。
Objective To investigate the oxidative damage induced by methylmercury (MeHg) in rat cerebral cortex and to explore the antagonistic effect of N-acetylcysteine (NAC) on oxidative damage induced by methylmercury in rat cerebral cortex. Methods Thirty-two healthy Wistar rats were randomly divided into four groups according to body weight: control (normal saline group), low dose (4μmol / kg) MeHg group, high dose (12μmol / kg) MeHg group and NAC mmol / kg) pretreatment + MeHg (12μmol / kg) group, 8 in each group, male and female. NAC pretreatment + MeHg group subcutaneously injected with NAC solution, the control group and low and high dose MeHg group were injected subcutaneously with normal saline; 2h after injection, by intraperitoneal injection of MeHg, continuous exposure to poisoning for 4 weeks, measured protein content of brain tissue thiol, Carbonyl and malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG) and the content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), adenosine triphosphate (ATP) Enzyme activity. Results The levels of MDA, protein carbonyl and 8-OHdG in the cerebral cortex of MeHg -treated rats were significantly increased (P <0.05), while the contents of sulfhydryl groups and the activities of SOD, GSH-Px and ATPase were decreased (P <0.05) Compared with high-dose MeHg group, the above indexes of cerebral cortex of NAC pretreatment + MeHg group were significantly improved (P <0.05). Conclusion MeHg can induce the oxidative damage of cerebral cortex in rats. NAC can antagonize the oxidative damage of cerebral cortex induced by methyl mercury in rats.