骨化三醇对MPTP诱导慢性帕金森病小鼠模型脑内神经递质的影响

目的探讨骨化三醇对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导慢性帕金森病小鼠模型脑内氨基酸类和单胺类神经递质的影响。方法C57BL／6小鼠随机分为对照组、模型组、骨化三醇高剂量给药组和低剂量给药组，构建MPTP慢性模型，应用高效液相色谱法测定中脑及纹状体内氨基酸类神经递质，包括天冬氨酸（Asp）、谷氨酸（Glu）、甘氨酸（Gly）、牛磺酸（Tau）、1，-氨基丁酸（GABA）和单胺类神经递质，包括多巴胺（DA）及其代谢产物3,4-双羟苯乙酸（DOPAC）的含量。结果与对照组相比，模型组小鼠氨基酸类神经递质除中脑内GABA外含量增加，纹状体内DA和DOPAC含量降低，代谢率增加俨〈O．01或P〈0．05）。骨化三醇给药组与模型组相比，高剂量可使中脑GIu，Gly，Tau及纹状体内五种氨基酸含量降低，DA和DOPAC含量增加，代谢率降低俨〈O．01或P〈0．05）；低剂量则仅可减缓中脑Tau和纹状体除Tau以外其他4种氨基酸含量增长状况。结论骨化三醇能改善MPTP所致慢性PD小鼠模型脑内神经递质含量异常，直接或间接保护DA能神经元，对其机制的深入研究有助于新型神经保护药物的开发。

Effects of Calcitriol on Neurotransmitters in Brain in the Chronic MPTP-induced Mice with Parkinson＇s Disease

Objective To investigate the effects of calcitriol on amino acid and monoamine neurotransmitters in brain in the chronic 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine （MPTP） -treated mice with Parkinson＇s disease （PD）. Methods C57BL/6 mice were randomly divided into control group, model group, high-dose calcitriol group and low-dose calcitriol group. Symptoms of PD were induced by intraperitoneal injection of MPTP. The contents of amino acid such as aspartate （Asp）, glutamic acid （Glu）, glycine （Gly）, taurine （Tau） and y-aminobutyric acid （GABA） as while as monoamine neurotransmitters such as dopamine （DA） and 3,4-dihydroxyphenylacetic acid （DOPAC） were detected by high performance liquid chromatography （HPLC）. Results After treated by MPTP, amino acid concentrations of mice in the model group revealed a significant increase except GABA in midbrain, while DA and DOPAC decreased significantly with metabolic rate increased （P 〈 0.01 or P 〈 0.05）. Compared with the model group, high doses of calcitriol could make Glu, Gly, Tau in midbrain and the five kinds of amino acid neurotransmitters in striatum decreased, DA and DOPAC contents increased while metabolic rate of DA decreased significantly （P〈0.01 or P〈0.05）. Only low doses of calcitriol could reduce Tau in midbrain and other four kinds of amino acids in striatum. Conclusion Calcitriol can markedly improve abnormality of neurotransmitter consents induced by MPTP in the chronic PD mice models, which protects DA neurons di- rectly or indirectly.