美金刚胺对甲基汞致大鼠谷氨酸代谢障碍及氧化损伤的影响

Effect of memantine on dysbolism of glutamate and oxidative injury induced by methylmercury in rats

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 explore the effect of memantine（MEM）on the dysbolism of glutamate and the oxidative injury induced by methylmercury exposure in rats.Methods Thirty Wistar rats were randomly divided into three groups,the first group was normal control,the second group was the methylmercury exposed group,the third group was the memantine-pretreated group.The first and second groups were subcutaneously injected with 0.9% NaCl,the third group was given 5 μmol/kg MEM in advance.Two hours,the first group was intraperitoneally injected with 0.9% NaCl,while the second and third groups were injected with 12μmol/kg methylmercury（5 ml/kg）.The pretreatment was given 3 times a week,and while the methylmercury administration was 5 times a week,the experiment lasted for 4 weeks.24 hours after the last injection,the Hg levels,activities of GS（glutamine synthetase）,PAG（phosphate activated glutaminase）,SOD（superoxide dismutase）and GSH-Px（glutathione peroxidase）,the contents of Glu（glutamic acid）and Gln（glutamine）,contents of GSH（glutathione）and MDA（malonaldehyde）,intracellular ROS and apoptosis rate in brain cortex were all determined.Results Compared with control group,the mercury content,Glu content and PAG activity increased significantly,while Gln content and the activities of GS,GSH,SOD and GSH-Px were all decreased,while MDA content and apoptosis rate were increased significantly in methylmercury exposed group.All these changes mentioned above in memantine pretreated group were all reduced.Conclusion The results suggested that memantine has a definite protective effect on the dysbolism of glutamate and oxidative injury caused by methylmercury exposure