mGluR5拮抗剂SIB-1893逆转6-OHDA抑制星形胶质细胞摄取谷氨酸的作用

目的 :研究亲代谢型谷氨酸受体 5 (mGluR5 )拮抗剂 (E) 2 甲基 6 (2 苯乙烯 )嘧啶 (SIB 1893)及6 羟基多巴胺 (6 OHDA)对星形胶质细胞摄取谷氨酸功能的影响。方法 :取新生大鼠脑星形胶质细胞作原代培养 ,根据 3 H]标记的D ,L 谷氨酸摄入量判断细胞的谷氨酸摄取功能。应用高效液相色谱法(HPLC)与荧光检测器联用的方法检测培养液中的谷氨酸水平 ;乳酸脱氢酶 (LDH)释放法测定细胞活力。结果 :6 OHDA呈浓度依赖性抑制星形胶质细胞谷氨酸摄取功能、降低细胞活力 ,但不诱导细胞释放谷氨酸 ;SIB 1893不影响正常星形胶质细胞的谷氨酸摄取量 ,但可以增加 6 OHDA损伤组的谷氨酸摄取量。结论 :6 OHDA的神经损伤机制可能与其抑制星形胶质细胞谷氨酸摄取功能有关 ,SIB 1893则能逆转 6 OHDA引起的谷氨酸摄取抑制效应 ,具有神经保护作用

SIB-1893 reversed 6-OHDA-induced inhibitory effect on glutamate uptake of astrocytes

AIM: To study the effect of (E) 2 methyl 6 (2 phenylethenyl)pyridine, the metabotropic glutamate receptor5(mGluR5) antagonist, and 6 hydroxydopamine (6 OHDA) on astrocytic glutamate uptake activity. METHODS: Rat cortical astrocytes from 1 to 2 days old rats were separated for primary culture. Glutamate uptake activity of astrocytes was determined, using isotopic techniques, by intracellular 3 H labeled D, L glutamate concentration. In addition, the extracellular glutamate concentration was assayed by high performance liquid chromatography(HPLC). Cell viability was assessed with the Lactate dehydrogenase(LDH) activity released into the incubation medium. RESULTS: 6 OHDA decreased astrocytic glutamate uptake in a concentration dependent manner, but it had no effect on inducing glutamate release from astrocytes. Cell viability was also decreased in a concentration dependent manner while LDH activity increased. SIB 1893 had no effect on normal astrocytic glutamate uptake,but increased glutamate uptake of impaired astrocytes caused by 6 OHDA. CONCLUSION: The neurotoxic mechanism of 6 OHDA may be associated with the decrease of astrocytic glutamate uptake activity. SIB 1893 can reverse the inhibitory effect induced by 6 OHDA on astrocytic glutamate uptake and therefore have neuroprotective effects.