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目的研究地卓西平马来酸盐(dizocilpine maleate,MK-801)和牛磺酸对大鼠甲基汞中毒所致的谷氨酸代谢紊乱的影响。方法将健康清洁级Wistar大鼠40只按体重随机分为对照组、低剂量甲基汞染毒组、高剂量甲基汞染毒组、MK-801+甲基汞染毒组和牛磺酸+甲基汞染毒组。,每组8只。对照组和低、高剂量甲基汞染毒组皮下注射生理盐水,MK-801+甲基汞染毒组和牛磺酸+甲基汞染毒组分别皮下注射0.3μmol/kgMK-801和1mmol/kg牛磺酸。注射2h后,对照组腹腔注射0.9%生理盐水,低剂量甲基汞染毒组腹腔注射4μmol/kg氯化甲基汞,高剂量甲基汞染毒组、MK-801+甲基汞染毒组和牛磺酸+甲基汞染毒组腹腔注射12μmol/kg氯化甲基汞。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、五注射MK-801和牛磺酸。测定各组大鼠大脑皮质汞含量、谷氨酸(Glu)和谷氨酰胺(Gln)含量以及谷氨酰胺合成酶(GS)和谷氨酰胺酶(PAG)活力。结果与对照组比较,高、低剂量甲基汞染毒组和MK-801+甲基汞染毒组、牛磺酸+甲基汞染毒组大鼠大脑皮质中汞含量均升高;高剂量甲基汞染毒组大鼠大脑皮质中Glu含量较高,GS活力较低;高、低剂量甲基汞染毒组大鼠大脑皮质中Gln含量较低,PAG活力较高,差异有统计学意义(P<0.01)。与高剂量甲基汞染毒组比较,MK-801+甲基汞染毒组和牛磺酸+甲基汞染毒组大鼠大脑皮质中汞含量无明显差异,Glu含量和PAG活力较低,Gln含量和GS活力较高,差异有统计学意义(P<0.01)。结论MK-801和牛磺酸对甲基汞所致大鼠谷氨酸代谢紊乱有一定的拮抗作用。
Objective To investigate the effects of dizocilpine maleate (MK-801) and taurine on the metabolic disorder of glutamate induced by methylmercury poisoning in rats. Methods Forty healthy Wistar rats were randomly divided into control group, low dose methylmercury exposure group, high dose methylmercury exposure group, MK-801 + methylmercury exposure group and taurine + Methylmercury exposure group. , Each group of 8. The control group and low and high dose methylmercury injection groups were injected subcutaneously with normal saline. MK-801 + methylmercury and taurine + methylmercury injection groups were subcutaneously injected with 0.3μmol / kg MK-801 and 1mmol / kg taurine. After injection for 2h, the control group was intraperitoneally injected with 0.9% physiological saline. The low dose methylmercury exposure group was injected intraperitoneally with 4μmol / kg methylmercury chloride, high dose methylmercury exposure group, MK-801 + methylmercury exposure Group and taurine + methylmercury poisoning group intraperitoneal injection of 12μmol / kg of methylmercury chloride. Continuous for 4 weeks, 5 days a week, daily exposure to methylmercury chloride once a week, one, three, five weekly injection of MK-801 and taurine. The contents of Hg, Glu and Gln and the activities of glutathione synthetase (GS) and glutaminase (PAG) in cerebral cortex of rats in each group were measured. Results Compared with the control group, the levels of mercury in the cerebral cortex of high and low dose methylmercury poisoning group and MK-801 + methylmercury exposure group and taurine + methylmercury exposure group were both increased; The rats in the methylmercury exposure group had higher levels of Glu and GS in the cerebral cortex, while those in the high and low doses of methylmercury exposure group had lower Gln content and higher PAG activity in the cerebral cortex Significance (P <0.01). Compared with the high dose methylmercury exposure group, there was no significant difference in the content of mercury in the cerebral cortex between the MK-801 + methylmercury exposure group and the taurine + methylmercury exposure group, while the Glu content and PAG activity were lower, Gln content and GS activity was higher, the difference was statistically significant (P <0.01). Conclusion MK-801 and taurine antagonize the disorder of glutamate metabolism induced by methylmercury in rats.