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目的:探讨抑制谷氨酰胺合成酶对小鼠纹状体氨基酸类递质和单胺类递质稳态的影响。方法:3月龄C57BL/6J小鼠,腹腔给予谷氨酰胺合成酶抑制剂L-蛋氨酸磺酸盐0.1 mL/10 g,隔日给药,持续2周。Western blot方法检测纹状体谷氨酰胺合成酶以及谷氨酸转运体蛋白表达水平,高效液相色谱法检测纹状体谷氨酸、谷氨酰胺等氨基酸类递质和多巴胺、5-羟色胺等单胺类递质的含量。结果:同生理盐水对照组相比,实验组小鼠纹状体谷氨酸转运体1、谷氨酸天冬氨酸转运体表达上调,谷氨酰胺合成酶表达下调;谷氨酸、谷氨酰胺、天冬氨酸含量减少,γ-氨基丁酸、丝氨酸含量增加,而单胺类递质含量无明显变化。结论:系统性给予谷氨酰胺合成酶抑制剂能影响脑内氨基酸类递质代谢的稳态,导致兴奋性神经递质谷氨酸水平下降,抑制性神经递质γ-氨基丁酸水平上升,但对单胺类递质含量没有影响。
Objective: To investigate the effects of glutamine synthetase on the steady state of neurotransmitters and monoamine neurotransmitters in striatum of mice. Methods: Three-month-old C57BL / 6J mice were intraperitoneally administered with 0.1 mL / 10 g L-methionine sulfonate as a glutamine synthetase inhibitor, and were administered on alternate days for 2 weeks. Western blot was used to detect the expression of glutamine synthetase and glutamate transporter protein in striatum. Amino acids such as glutamate, glutamine and dopamine, 5-hydroxytryptamine Monoamine neurotransmitters content. Results: Compared with the saline control group, the expression of glutamate transporter 1 and glutamate aspartate transporter and the expression of glutamine synthetase in the striatum were decreased in experimental group; Amide, aspartic acid content decreased, γ-aminobutyric acid, serine content increased, while monoamine neurotransmitter content no significant change. CONCLUSIONS: Glutamine synthase inhibitors can affect the homeostasis of amino acid neurotransmitters in the brain, leading to the decrease of glutamate levels of excitatory neurotransmitters and the increase of γ-aminobutyric acid, an inhibitory neurotransmitter, However, monoamine neurotransmitter content has no effect.