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目的探讨盐酸美金刚胺(memantine hydrochloride,MEM)对甲基汞所致谷氨酸代谢障碍以及氧化损伤的影响。方法实验用Wistar大鼠30只,按体重随机分成3组。第1组为对照组,第2组为单纯染汞组,第3组为MEM预处理组。对照组和单纯染汞组皮下注射生理盐水,MEM预处理组皮下注射5μmol/kg MEM;2 h后,对照组腹腔注射生理盐水,单纯染汞组和MEM预处理组腹腔注射12μmol/kg氯化甲基汞,注射容量为5 ml/kg。干预隔日一次,每周3次,染毒每日1次,每周5次,连续干预与染毒4周。于最后一次染毒24 h后每组取6只大鼠,麻醉后处死,测定大脑皮质汞含量,谷氨酸(Glu)、谷氨酰胺(Gln)含量,谷氨酰胺合成酶(GS)、磷酸活化的谷氨酰胺酶(PAG)活力,还原型谷胱甘肽(GSH)、丙二醛(MDA)含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力。每组其余4只大鼠,制备大脑皮质单细胞悬液,测定活性氧簇(ROS)含量以及细胞凋亡率。结果与对照组比较,单纯染汞组大鼠大脑皮质汞含量显著升高,Glu含量及PAG活力显著升高,Gln含量及GS活力显著降低;GSH含量、SOD及GSH-Px活力显著降低,MDA含量显著升高;细胞内ROS含量及细胞凋亡率显著升高。MEM预处理组大脑皮质汞含量与单纯染汞组相比差异无统计学意义,其余指标均得到不同程度的拮抗,差异有统计学意义。结论 MEM对甲基汞导致的谷氨酸代谢障碍以及氧化损伤具有一定的保护作用。
Objective To investigate the effect of memantine hydrochloride (MEM) on glutamate metabolism and oxidative damage induced by methylmercury. Methods Thirty Wistar rats were randomly divided into three groups according to body weight. The first group was control group, the second group was simple mercury group, the third group was MEM pretreatment group. The control group and the simple mercury group were subcutaneously injected with normal saline, and the MEM pretreatment group was subcutaneously injected with 5 μmol / kg MEM. After 2 h, the control group was intraperitoneally injected with 12 μmol / kg chloride Methylmercury injection volume of 5 ml / kg. Intervention once every other day, 3 times a week, once a day, once a week, 5 times a week, continuous intervention and exposure for 4 weeks. Six hours after the last exposure, 6 rats in each group were killed after anesthesia, and the levels of mercury, glutamine, glutamine, glutamine synthetase, (PAG), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH- Px) vitality. The remaining four rats in each group were used to prepare single-celled suspension of cerebral cortex and the content of reactive oxygen species (ROS) and apoptosis rate were determined. Results Compared with the control group, the content of mercury and the activity of glutathione peroxidase (PAG) in Glomerulus significantly increased, while the Gln content and GS activity decreased significantly. The activities of GSH, SOD and GSH-Px decreased significantly Content was significantly increased; intracellular ROS content and apoptosis rate was significantly increased. There was no significant difference in the content of mercury in cerebral cortex between MEM pretreatment group and pure mercury group, and the other indexes were all antagonized in different degrees with statistical significance. Conclusion MEM can protect against glutamate-induced glutamate metabolism and oxidative damage.