文章摘要
郑 慧,宋南姗,丁建花,肖 明,胡 刚.抑制谷氨酰胺合成酶对小鼠纹状体氨基酸类和单胺类递质含量的影响[J].南京医科大学学报,2017,(4):389~393
抑制谷氨酰胺合成酶对小鼠纹状体氨基酸类和单胺类递质含量的影响
Effects of glutamine synthetase inhibitor on the concentrations of amino acid neurotransmitters and monoamine neurotransmitters in the striatum of mice
投稿时间:2017-01-04  
DOI:10.7655/NYDXBNS20170401
中文关键词: 谷氨酰胺合成酶  谷氨酸  γ-氨基丁酸
英文关键词: glutamine synthetase  glutamate  γ-aminobutyric acid
基金项目:国家自然科学基金(81473196)
作者单位
郑 慧 南京医科大学基础医学院药理学系江苏省神经退行性疾病重点实验室江苏 南京 211166 
宋南姗 南京医科大学基础医学院药理学系江苏省神经退行性疾病重点实验室江苏 南京 211166 
丁建花 南京医科大学基础医学院药理学系江苏省神经退行性疾病重点实验室江苏 南京 211166 
肖 明 南京医科大学基础医学院药理学系江苏省神经退行性疾病重点实验室江苏 南京 211166 
胡 刚 南京医科大学基础医学院药理学系江苏省神经退行性疾病重点实验室江苏 南京 211166 
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中文摘要:
      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。
英文摘要:
      Objective:To explore the effects of glutamine synthetase (GS) inhibitor on the homoeostasis of amino acid neurotransmitters and monoamine neurotransmitters in the striatum of mice. Methods:Three-month-old C57BL/6J mice were intraperitoneally injected with glutamine synthetase inhibitor-methionine sulfoximine (MSO) for 2 weeks (0.1 mL/10 g,qod). The protein levels of GS and glutamate transporters were detected by Western blot. The concentrations of amino acid neurotransmitters (glutamic acid and glutamine) and monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) in the striatum were measured by high performance liquid chromatography. Results:Compared with the saline control group,MSO effectively inhibited GS protein expression and increased the levels of glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter) in the striatum. Mice with MSO injection exhibited lower levels of glutamate,glutamine and aspartic acid,and higher levels of γ-aminobutyric acid and serine,but showed no change in the concentrations of monoamine neurotransmitters. Conclusion:Systematical inhibition of glutamine synthetase could affect the homoeostasis of metabolism of amino acid neurotransmitters in the brain of mouse,and lead to the decrease of the excitatory neurotransmitter glutamate level and the increase of inhibitory neurotransmitter γ-aminobutyric acid level.
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