鱼藤酮对大鼠纹状体谷氨酸转运体及谷氨酰胺合成酶的影响

Toxic effects of Rotenone on glutamate transporter and glutamine synthetase in rat brain

目的研究鱼藤酮染毒大鼠纹状体谷氨酸转运体表达及谷氨酰胺合成酶活性的变化。方法应用HPLC荧光法检测鱼藤酮染毒大鼠纹状体谷氨酸(glutamate,Glu)浓度,RT-PCR与Western blot技术观察谷氨酸转运体基因及蛋白表达的变化,采用谷氨酰胺合成酶检测试剂盒观察其活性。结果1.2mg/kg鱼藤酮染毒大鼠纹状体Glu浓度明显升高,谷氨酸/天冬氨酸转运体(glutamate/aspartate transporter,GLAST)基因和蛋白表达均显著降低,而谷氨酸转运体-1(gluta-mate transporter-1,GLT-1)蛋白表达升高,谷氨酰胺合成酶(glutamine synthetase,GS)活性明显增强。结论GLAST表达下调可能是鱼藤酮诱导脑内谷氨酸含量增加的主要原因之一,而GLT-1上调及GS活性增强可能为神经细胞自我保护机制,以限制谷氨酸的神经毒作用。

Objective To thetase in rat brain. Methods study the toxic effects of Rotenone on glutamate transporter and glutamine synThe glutamate levels in the striatum of SD rats were detected by high performance liquid chromatography （ HPLC）, the expression of glutamate tansporter mRNA and proteins were detected by RT-PCR and Western blotting and the activity of glutamine synthetase was determined by using GS detect kit. Results Rotenone was shown to increase the release of glutamate in rat striatum, the expression of glutamate/aspartate transporter （GLAST） mRNA and protein decreased significantly in 0.6 mg/kg and 1.2 mg/kg Rotenone intoxicated groups, but the expression of GLT-1 and the activity of GS enhanced obviously. Conclusion Down-regulation of GLAST may be responsible for increased Glu level in rat brain induced by Rotenone, but the increased expression of GLT-1 and GS, activity may represent a protective mechanism of the brain cells by limiting the neurotoxicity of Glu.