N-乙酰半胱氨酸对甲基汞致大鼠脑皮质氧化损伤和谷氨酸代谢障碍的影响

Effect of N-acetylcysteine on oxidative damage and glutamate metabolic dysfunction of cerebrum in rats exposed to methylmercury

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 study the relationship between oxidatie damage and glutamate metabolic dysfunction induced by methylmercury in rats neural system,and to investigate the protective effect of NAC on neurotoxicity.Methods 40 Wistar rats were randomly divided into four groups,which were control group,4,12μmol/kg MeHg group and NAC pretreatment group.Groups 1~3 were injected with physiological saline,group 4 subcutaneous 1mmol/kg NAC.After 2 h,group 1 was given intraperitioneal injection of saline,and group 2 and 3 were givern intraperitioneal injection of 4,12μmol/kg MeHg,and group 4 was givern intraperitioneal injection of 12 μmol/kg MeHg.The doses are 5 ml/kg.NAC Intervention every other day and MeHg exposure once a day for 4 weeks,24 h after the last explour,the rats were killed and get the brain contex and determine the levels of mercury,GSH,MDA,Glu,Gln,ROS and the activity of SOD,GSH-Px,PAG,GS and the apoptosis rate.Results With the increase of mercury dose,the mercury of cerebral cortex increased,GSH and Gln decreased,MDA,Glu and ROS increased,the activities of SOD,GSH-Px and GS were reduced,PAG activity increased,the apoptosis rate increased.Compared with high-dose mercury group,NAC pretreatment group showed varying degrees of antagonism to neurotoxicity of MeHg.Conclusion Methylmercury can lead to brain oxidative damage and glutamate metabolic dysfunction,which were interrelated and promote each other.NAC has certain protective effect on the neurotoxicity-induced by methyl mercury.