I组mGluRs反义寡核苷酸抗谷氨酸对小鼠大脑皮层神经元的兴奋毒作用

THE PROTECTlVE EFFECTS OF GROUP I mGluRs ANTISENSE OLlGONUCLEOTlDES AGAINST NEUROTOXICITY OF SODIUM GLUTAMATE ON CULTURED MOUSE CEREBRAL CORTlCAL NEURONS

目的:研究I组代谢型谷氨酸受体(mGluRs)反义寡核苷酸对谷氨酸钠(Glu)引起的小鼠大脑皮层神经元损伤的保护作用。方法:以细胞乳酸脱氢酶(LDH)漏出、光镜下细胞形态变化为指标,观察培养液中加入Glu引起的神经元损伤及mGluRl反义寡核苷酸或mGluR5反义寡核苷酸的保护作用;用免疫细胞化学检测神经元mGlulα仪和mGluR5表达。结果:实验显示0.1mmol.L-1的谷氨酸钠可明显造成神经元损伤,使LDH漏出增加(P<0.01),mGluRl反义寡核苷酸或mGluR5反义寡核苷酸6μmol.L-1和8μmol.L-1可明显拮抗Glu引起的神经元损伤,使LDH漏出显著减少(P<0.01);免疫组化实验证实体外培养神经元mGluRlα和mGluR5阳性表达。结论:mGluRl反义寡核苷酸和mGluR5反义寡核苷酸可对抗Glu引起的皮层神经元损伤。

To investigate the protective effect of mGluR1 antisense oligonucleotides and mGluR5 anti,sense oligonucleotides on impairment of cultured mouse cerebral cortical neurons induced by sodium glutamate（Glu）. Methods： Neuron damage induced by Glu as well as the action of mGluR1 antisense oljgonucleotides and mGluR5 antisense oligonucleotides were measured by determining the leakage of lactate dehydrogenase （LDH）from neurons. Immunocytochemistry method was used to detect the expression of anti- mGluR1α and anti-mGluR5, Morphological changes of primary cortical neurons were observed by phase contrast microscope. Results： Following the exposure of the cells to 0.1 mmol. L^- 1 Glu for 15 min, LDH leakage from neurons increased, mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides（6 or 8 μmol. L^-1 ）as well as 50 μmol. L^- 1 LY367385 reduced the LDH leakage. mGluR1α and mGluR5 immunopositive cells showed in cultured neurons. Conclusion： The protective effects of mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides on neurons damaged by Glu may rdate to antagonizing mGluR1α or mGItlR5.