利鲁唑对氯化锰致大鼠神经兴奋毒性的影响  

Antagonism of Riluzole to Excitotoxicity Induced by Manganese Chloride in Rats

作　　者：邓宇[1] 徐兆发[1] 田雅文[1] 徐斌[1] 辛辛[1] 邓小强[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：《环境与健康杂志》2009年第6期478-481,共4页Journal of Environment and Health

基　　金：国家自然科学基金资助项目(30771834);辽宁省教育厅科学研究基金资助项目(2004C025)

摘　　要：目的研究氯化锰对大鼠脑纹状体内谷氨酸-谷氨酰胺循环(Glu-Glncycle)和细胞凋亡的影响,并探讨利鲁唑对锰神经兴奋毒性的拮抗作用。方法将27只Wistar大鼠按体重随机分成3组,每组9只。对照组、单纯染锰组均皮下注射0.9%NaCl;利鲁唑预处理组皮下注射21.35μmol/kg利鲁唑。2h后,对照组腹腔注射0.9%NaCl,单纯染锰组、利鲁唑预处理组腹腔注射200μmol/kgMnCl2。干预并染毒4周,每周5次。最后一次干预并染毒24h后,首先每组取6只大鼠麻醉后处死,分离脑纹状体,测定其内Glu和Gln的含量及谷氨酰胺合成酶(GS)和磷酸激活的谷氨酰胺酶(PAG)的活力;再取各组剩余大鼠的纹状体组织制备成单细胞悬液,用流式细胞仪检测细胞凋亡情况。结果与对照组相比,在单纯染锰组中,Glu含量升高,Gln含量降低(均P<0.01);GS活力降低,PAG活力升高(均P<0.01)。与单纯染锰组相比,在利鲁唑预处理组中,Glu含量降低,Gln含量升高(均P<0.05);GS活力升高,PAG活力下降(均P<0.05)。与对照组相比,在单纯染锰组中,细胞总、早期及晚期凋亡率均明显增加(均P<0.01)。与单纯染锰组相比,在利鲁唑预处理组中,细胞总、早期及晚期凋亡率均明显降低(P<0.01,P<0.05)。结论氯化锰可以破坏大鼠脑纹状体内Glu-Glncycle并导致细胞凋亡,利鲁唑对锰神经兴奋毒性具有一定的拮抗作用。Objective To observe the effect of MnCl2 on glutamate-glutamine cycle （Glu-Gin cycle） and apoptosis of dissociated striatum cells and to approach the antagonism of riluzole to the neurotoxicity of MnCl2. Methods Twenty-seven Wistar rats were randomly divided into 3 groups, 9 in each. The first group was the control group and the second group was the single MnCl2 exposure group. Both of the groups were injected with 0.9% NaCl subcutaneously （sc）. The third group was the intervention group and was injected with 21.35 μmol/kg riluzole （sc）. Two hours later, the rats in the control group were the given 0.9% NaCl intraperitoneally （ip） injection, the second and third groups were injected with 200 μmol/kg MnCl2 （ip）, five times a week, for 4 weeks. Twenty-four hours after the last injection, 6 rats in each group were killed and the contents of Glu and Gin, the activities of glutamine synthetase （GS） and phosphate activated glutaminase （PAG） in the striatum of the rats were determined. The apoptosis of the dissociated striatum ceils was detected in the other rats in each group by flow cytometry （FCM） technique. Results Compared with the control group, in MnCl2 group, the content of Glu increased and Gin content decreased significantly （P〈0.05, P〈0.01） and the activity of GS decreased and PAG activity increased （P〈0.05, P〈0.01）. Compared with. MnCl2 group, in riluzole group, the content of Glu decreased and Gin increased （P〈0.05, P〈0.01） and the activity of GS increased and PAG activity decreased （P〈0.01, P〈0.05）. Compared with the control group, in MnCl2 group, the total, early and late apoptosis rates of the dissociated striatum cells increased （P〈0.01）. Compared with MnCl2 group, in riluzole group, the total, early and late apoptosis rates of the dissociated striatum cells decreased （P〈0.05, P〈0.01）. Conclusion MnCl2 exposure can cause Glu-Gln cycle destroyed and apoptosis in the striatum. Riluzole has a certain antagonistic effect on exci

关 键 词：金属 重 锰 利鲁唑 神经兴奋毒性 

分 类 号：R994.6[医药卫生—毒理学]