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目的研究甲基汞致大鼠脑氧化损伤与谷氨酸代谢障碍的关系,探讨N-乙酰半胱氨酸(NAC)对甲基汞致大鼠神经毒性的防护作用。方法 40只Wistar大鼠按体重随机分成4组:对照组、4和12μmol/kg MeHg组及NAC预处理组。第1～3组皮下注射生理盐水,第4组皮下注射1 mmol/kg NAC;2 h后,第1组腹腔注射生理盐水,第2和3组分别腹腔注射4和12μmol/kg MeHg,第4组腹腔注射12μmol/kg MeHg,注射剂量均为5 ml/kg。干预隔日1次,染毒每日1次,连续干预与染毒4周。最后一次染毒24 h后,处死大鼠取其大脑皮质,测定汞、GSH、MDA、Glu、Gln、ROS含量,SOD、GSH-Px、PAG、GS活力,以及细胞凋亡率。结果随着染汞剂量的增大,脑皮质汞的含量也随之增大,GSH和Gln的含量降低,MDA、Glu和ROS的含量升高,SOD、GSH-Px和GS的活力降低,PAG的活力升高,细胞凋亡率增大;NAC预处理组与高剂量染汞组比较,上述指标均得到不同程度的拮抗。结论甲基汞可导致脑氧化损伤和谷氨酸代谢障碍,二者相互联系、相互促进;NAC对甲基汞所致氧化损伤和谷氨酸代谢障碍具有一定的防护作用。
Objective To investigate the relationship between brain oxidative damage and glutamate metabolism induced by methylmercury in rats and the protective effect of NAC on neurotoxicity induced by methylmercury in rats. Methods Forty Wistar rats were randomly divided into four groups according to body weight: control group, 4 and 12μmol / kg MeHg group and NAC preconditioning group. Groups 1 to 3 were injected subcutaneously with normal saline and group 4 subcutaneously with 1 mmol / kg NAC. After 2 hours, group 1 received intraperitoneal injection of saline, groups 2 and 3 received intraperitoneal injections of 4 and 12 μmol / kg MeHg, and group 4 Group intraperitoneal injection of 12μmol / kg MeHg, the injection dose was 5 ml / kg. Intervention 1 time every other day, once daily exposure, continuous intervention and exposure for 4 weeks. The rats were sacrificed 24 h after the last exposure, and the contents of Hg, GSH, MDA, Glu, Gln, ROS, SOD, GSH-Px, PAG and GS were measured. Results As the dose of mercury was increased, the content of mercury in cerebral cortex increased, the content of GSH and Gln decreased, the content of MDA, Glu and ROS increased, the activity of SOD, GSH-Px and GS decreased, The vitality increased, the apoptosis rate increased; NAC pretreatment group and high-dose mercury group compared to the above indicators were different levels of antagonism. Conclusions Methylmercury can cause cerebral oxidative damage and glutamate metabolism, which are interrelated and mutually reinforcing. NAC can protect against methylmercury-induced oxidative damage and glutamate metabolism.