小剂量NMDA对谷氨酸兴奋性神经毒性作用的拮抗及机制研究  

STUDY ON MECHANISM OF SUBTOXIC CONCENTRATION OF NMDA INDUCED NEUROPROTECTION AGANIST GLUTAMATE NEUROTOXICITY IN CULTURED NEURONS IN RAT

作　　者：梁英武[1,2] 单巍松[1,2] 张国荣 王朝晖[1,2] 吴希如 

机构地区：[1]济宁医学院儿科学教研室 [2]北京医科大学第一医院

出　　处：《济宁医学院学报》1998年第2期1-4,共4页Journal of Jining Medical University

基　　金：国家自然科学基金

摘　　要：目的观察小剂量ＮＭＤＡ对谷氨酸兴奋性神经毒性作用的拮抗作用及其机制。方法以体外培养的胚胎大鼠大脑皮层神经元为对象，利用细胞生物学、生物化学以及统计学（方差分析）等技术比较观察不同因素处理后细胞生物学及生化方面的改变。结果０５ｍｏｌ／Ｌ谷氨酸作用神经元３０ｍｉｎ后可引起细胞死亡及ＬＤＨ释放增加，预先２ｈ给予亚致死剂量的ＮＭＤＡ（１００μｍｏｌ／Ｌ）能明显阻断上述作用，如果在ＮＭＤＡ给予前５ｍｉｎ分别加入ＭＫ－８０１、ＣＣＫ抗血清、ＣＣＫＢ、Ａ受体拮抗剂Ｌ－３６５２６０、Ｌ－３６４７１８及联合给予ｃ－ｆｏｓ、ｃ－ｊｕｎ反义寡聚核苷酸，前３种药物能明显阻断ＮＭＤＡ的神经毒性保护作用，而Ｌ－３６４７１８及反义ｃ－ｆｏｓ和ｃ－ｊｕｎ抑制不明显。结论小剂量ＮＭＤＡ对谷氨酸兴奋性神经毒性作用具有拮抗作用，其机制可能与促进内源性ＣＣＫ释放或合成增加有关，ｃ－ｆｏｓ、ｃ－ｊｕｎ参与并介导了ＮＭＤＡ诱导ＣＣＫ合成过程。Objective To explore the mechanism of the subtoxic concentration of NMDA induced neuroprotection aganist glutamate neurotoxicity in the cultured neurons in rat.Methods The viabilities of the cultured neurons and the concentrations of LDH which released from the cultured neurons that were treated by various factors were examined with cellular biological and chemical technology.Results To expose the cultured neurons to glutamate(500 μmol/L,30min)results:neurotoxicity, pretreatment of meurons with subtoxic concentration of NMDA may markedly antagonize the neurotoxic action of glutamate,the neuropretective effects of NMDA were blocked party by MK-801,anti serum and receptor antagonist L-365260 of CCK. Conclusion The neuroprotection of NMDA aganist glutamate neurotoxicity may be due to enhancing endogenous CCK.

关 键 词：谷氨酸 毒性 NMDA CCK 保护作用 

分 类 号：R977.4[医药卫生—药品] R965.3[医药卫生—药学]