右美沙芬对甲基汞致大鼠神经损伤作用的影响  

Effect of dextromethorphan on the neurotoxicity of methyl mercury in rats

作　　者：辛辛[1] 徐兆发[1] 邓小强[1] 田雅文[1] 胡月明[1] 李茵[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生学教研室,辽宁沈阳110001

出　　处：《中国工业医学杂志》2009年第6期410-412,共3页Chinese Journal of Industrial Medicine

摘　　要：目的观察右美沙芬对甲基汞致神经损伤作用的影响。方法实验用Wistar大鼠32只,按体重随机分成4组,每组8只。第1组为对照组,第2、3组为不同剂量氯化甲基汞(methyl-mercuric chloride,MMC)染毒组,第4组右美沙芬(dextromethorphan,DM)干预组。实验开始时第1、2、3组大鼠皮下注射0.9%氯化钠溶液,第4组皮下注射DM13.5μmol/kg 2 h后,第1组腹腔注射0.9%氯化钠溶液,第2组腹腔注射4μmol/kg MMC溶液,第3、4组腹腔注射12μmol/kg MMC溶液,注射容量均为5 ml/kg,每周染毒5 d,每天1次,共4周(20次),但右美沙芬系隔日注射1次,每周3次,共12次,实验结束后24 h测定大脑皮质谷氨酰胺合成酶(GS)和磷酸活化的谷氨酰胺酶(PAG)活力、丙二醛(MDA)含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力。结果随着MMC剂量的增加,大鼠大脑皮质中GS活力降低,PAG活力升高,MDA含量升高,SOD和GSH-Px活力降低,与12μmol/kg MMC组相比,DM干预组大脑皮质中GS活力升高,PAG活力降低,MDA含量降低,SOD和GSH-Px活力升高。结论甲基汞可以干扰大鼠大脑皮质内"谷氨酸-谷氨酰胺循环(Glu-Gln cycle)",并可能引起氧化损伤;右美沙芬对甲基汞的神经毒性及其氧化损伤作用具有一定的拮抗能力。Objective To explore the effect of dextromethorphan（DM）on the neurotoxicity induced by methyl mercury.Methods Thirty-two Wistar rats were randomly divided into 4 groups,which were control group,low dose of methyl-mercuric chloride（MMC）group,high dose of MMC group and DM intervention group;8 rats in each group.Rats in the former three groups were subcutaneously（sc）injected with 0.9% NaCl,rats in fourth group were sc.injected with 13.5 μmol/kg DM,every other day for four weeks（12 times）.Two hours later,the control rats were intraperitoneally（ip）injected with 0.9% NaCl,rats of second group were injected with 4 μmol/kg MMC,rats of third and fourth group were injected with 12 μmol/kg MMC,five times a week,for 4 weeks.Twenty-four hours after the last injection,rats were sacrificed,content of malondialdehyde（MDA）as well as the activities of glutamine synthetase（GS）,phosphate activated glutaminase（PAG）,superoxide dismutase（SOD）and glutathione peroxidase（GSH-Px）in cerebral cortex of rat were determined.Results Compared with control group,cerebral cortex contents of MDA and the activity of PAG in MMC treated group were increased,the activities of GS,SOD and GSH-Px in cerebral cortex of rat were decreased;while the contents of MDA and the activity of PAG in DM group were decreased,and the activities of GS,SOD and GSH-Px in the cortex of rat were increased compared with those of MMC treated group.Conclusions The results suggested that methyl mercury might disturb the＂Glutamate and Glutamine Cycle＂in cerebral cortex and induce oxidative damage and dextromethorphan might have antagonistic ability on the neurotoxicity and oxidative damage of MMC in rats.

关 键 词：甲基汞 右美沙芬 神经毒性 氧化损伤 

分 类 号：R994.6[医药卫生—毒理学]