右美沙芬和利鲁唑对甲基汞染毒大鼠神经毒性的影响

目的研究右美沙芬(dextromethorphan,DM)和利鲁唑(riluzole)对甲基汞染毒大鼠神经毒性的影响。方法将健康清洁级Wistar大鼠28只按体重随机分为对照组、氯化甲基汞组、右美沙芬+氯化甲基汞组、利鲁唑+氯化甲基汞组,每组7只。对照组和氯化甲基汞组皮下注射生理盐水溶液,右美沙芬+氯化甲基汞组和利鲁唑+氯化甲基汞组分别皮下注射13.5μmol/kg右美沙芬、21.35μmol/kg利鲁唑。注射2h后,对照组腹腔注射生理盐水,氯化甲基汞组、右美沙芬+氯化甲基汞组、利鲁唑+氯化甲基汞组腹腔注射氯化甲基汞溶液12.0μmol/kg,注射容量均为5ml/kg。连续进行4周,每周5天,每天染毒氯化甲基汞1次,每周一、三、五染毒右美沙芬、利鲁唑。测定大脑皮质中汞(Hg)、谷氨酰胺(Gln)、谷氨酸(Glu)含量以及小脑中琥珀酸脱氢酶(SDH)、Na+-K+-ATP酶、Ca2+-ATP酶活力。结果与对照组相比,氯化甲基汞组大脑皮质中Hg、Glu含量上升,Gln含量降低,小脑中SDH和Na+-K+-ATP酶、Ca2+-ATP酶活力降低,差异均有统计学意义(P0.05或P0.01)。与氯化甲基汞组相比,右美沙芬+氯化甲基汞组和利鲁唑+氯化甲基汞组大脑皮质Hg、Glu含量降低,Gln含量升高,SDH、Na+-K+-ATP酶和Ca2+-ATP酶活力升高,差异均有统计学意义(P0.05或P0.01)。结论甲基汞可扰乱谷氨酸-谷氨酰胺循环,右美沙芬和利鲁唑对甲基汞神经毒性具有一定的拮抗作用。

Antagonism of Dextromethorphan and Riluzole to Neurotoxicity Induced by Methylmercury in Rats

Objective To observe the adverse effect of methylmercury on the cortex and cerebellum respectively as well as to approach the antagonisms of dextromethorphan (DM) and riluzole to the mercury-induced neurotoxicity. Methods Twenty-eight Wistar rats were randomly divided into 4 groups by weight,'/in each. The first group was the control group and the second group was methylmercuric chloride (MMC) group. The third and fourth groups were DM and riluzole group respectively. Both of the former groups were subcutaneously injected with saline. The third and fourth groups were subcutaneously injected with 13.5 μmol/kg DM and 21.35 μmol/kg respectively every other day. Two hours later,the animals in the control group were intraperitoneally given the injection of saline. From the second to fourth groups were injected with 12.0 μmoi/kg MMC. The administration of MMC above was given five times a week(from Monday to Friday), for 4 weeks as well as the administration of DM and riluzole every other day before injected with MMC (on Monday,Wednesday and Friday). Twenty-four hours after the last injection,7 rats in each group were sacrificed. The contents of Hg, Ca~(2+)-ATPase in the cerebellum were determined. Results In MMC group, the contents of Hg, Glu and the content of Gin were decreased, the activities of SDH, Na~+-K~+-ATPase and Ca~(2+)-ATPase were decreased compared with the control group. Compared with MMC group,in DM and riluzole groups,the contents of Hg,Glu decreased, the content of Gn increased, moreover, the activities of SDH, Na~+-K~+-ATPase and glutamate(Glu), glutamine (Gin) in the rat cortex and the activities of SDH, Na~+-K~+-ATPase and Ca~(2+)-ATPase increased significantly. Conclusion "Glu-Gln Cycle" can be destroyed by MMC, DM and liluzole present some antagonistic effects on MMC-indused neurotoxicity in rats.