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[目的]观察鱼藤酮(rotenone)对大鼠纹状体谷氨酸-谷氨酰胺环路代谢的影响。[方法]将24只SD大鼠随机分为正常对照组、溶剂对照组、2.0mg/kg和4.0mg/kg鱼藤酮染毒组。采用高效液相色谱法(HPLC)检测鱼藤酮染毒大鼠纹状体谷氨酸(glutamate,Glu)和谷氨酰胺(glutamine,Gln)含量;使用逆转录聚合酶链式反应(RT-PCR)法观察谷氨酰胺合成酶(glutamine synthetase,GS)基因表达的变化;采用分光光度法检测谷氨酰胺酶(phosphate activated glutaminase,PAG)与GS活性。[结果]与正常对照组比较,4.0mg/kg染毒组大鼠纹状体Glu含量明显升高(P<0.01),而Gln含量明显降低(P<0.01);4.0mg/kg染毒组GS mRNA表达明显增强(P<0.05);4.0mg/kg染毒组GS活性却明显降低,PAG活性明显升高(P<0.01)。[结论]鱼藤酮诱导大鼠纹状体Glu含量明显升高,可能是导致中脑神经元兴奋性损伤的的主要原因之一。
[Objective] To observe the effect of rotenone on glutamate-glutamine cycle metabolism in rat striatum. [Method] 24 SD rats were randomly divided into normal control group, solvent control group, 2.0 mg / kg and 4.0 mg / kg rotenone group. The levels of glutamate (Glu) and glutamine (Gln) in the striatum of rotenone-exposed rats were detected by high performance liquid chromatography (HPLC). Reverse transcription polymerase chain reaction The changes of glutamine synthetase (GS) gene expression were observed by enzyme linked immunosorbent assay (ELISA). The levels of PAG and GS were measured by spectrophotometry. [Result] Compared with the normal control group, the content of glutamate in the striatum of 4.0 mg / kg exposure group was significantly increased (P <0.01), while the content of Gln was significantly decreased (P <0.01); 4.0 mg / kg exposure group GS mRNA expression was significantly increased (P <0.05). The GS activity was significantly decreased and the PAG activity was significantly increased in 4.0 mg / kg group (P <0.01). [Conclusion] The content of Glu in striatum induced by rotenone is obviously increased, which may be one of the main causes of the excitotoxic injury of midbrain neurons.