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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 investigate the effects of manganese chloride on glutamate-glutamine cycle (GLUT) and apoptosis in rat striatum and to explore the antagonistic effect of riluzole on excitotoxicity of manganese nerve. Methods Twenty-seven Wistar rats were randomly divided into 3 groups according to body weight, with 9 rats in each group. The control group and pure manganese group were subcutaneously injected with 0.9% NaCl. The riluzole pretreatment group was subcutaneously injected with riluzole 21.35μmol / kg. After 2 hours, the control group was intraperitoneally injected with 0.9% NaCl, and the rats in the manganese-only group and the riluzole preconditioning group were intraperitoneally injected with 200μmol / kg MnCl2. Intervention and poisoning 4 weeks, 5 times a week. After the last intervention and exposure for 24 hours, six rats in each group were anesthetized and sacrificed. The striatum was isolated and the levels of Glu and Gln and glutamine synthetase (GS) and phospho-activated glutamine Amidase (PAG) activity; then take the rest of the rat striatum tissue prepared single cell suspension, flow cytometry was used to detect apoptosis. Results Compared with the control group, the contents of Glu and Gln decreased (P <0.01). GS activity decreased and PAG activity increased (all P <0.01). Compared with manganese alone group, in the riluzole preconditioning group, Glu content and Gln content increased (all P <0.05); GS activity increased and PAG activity decreased (all P <0.05). Compared with the control group, in the group of pure manganese, the total cell apoptosis rates in both early and late stages were significantly increased (all P <0.01). Compared with pure manganese group, in the riluzole pretreatment group, the total cell apoptosis rate in early and late stage were significantly decreased (P <0.01, P <0.05). Conclusion Manganese chloride can damage Glu-Glncycle in rat brain striatum and lead to apoptosis. Riluzole can antagonize the excitotoxicity of manganese nerve.