【摘要】 目的　探讨兴奋性氨基酸受体拮抗剂磷酸甲基谷氨酰氨酸 (GAPA)对胆红素神经毒性的影响。方法　在制作胆红素脑病动物模型基础上予GAPA干预 ,观察对照组、模型组、模型干预组新生豚鼠 (每组 10只 )干预后 4、8h脑组织超微结构、脑组织ATP含量与含水量。结果　模型组脑组织ATP含量在 4、8h分别为 (2 .7± 0 .7) μmol/g与 (2 3± 0 7) μmol/g,显著低于对照组 (4 3± 0 6 )μmol/g与 (4 1± 0 6 ) μmol/g ;GAPA干预组脑组织ATP含量在干预后 4、8h分别为 (2 6± 0 9) μmol/g与 (2 5± 0 8) μmol/g,显著低于对昭组 ,但与模型组比较 ,差异无显著性。胆红素脑病脑组织含水量显著增高 ,GAPA显著减轻胆红素毒性脑水肿 ,脑组织超微结构变化亦与此相符。结论　沉积于脑组织胆红素可抑制神经元能量代谢 ,致脑细胞水肿 ;兴奋性氨基酸受体拮抗剂GAPA可减轻脑水肿 ,但不影响能量代谢变化 ,其作用环节介于能量代谢变化与脑水肿之间。更多还原

【Abstract】 Objective To explore the effect of NMDA receptor antagonist glutamyl amino methyl phosphonic acid (GAPA) on the bilirubin neurotoxicity. Methods On the basis of bilirubin induced encephalopathy model in guinea pig, 10 μg/g of GAPA was injected intraperitoneal. After 4 and 8 hours the ATP content in the rat brain tissue was measured with fluorescence assay, and the degree of the brain edema was assessed by wet/dry weight ratios of the brain tissue. The ultrastructure change in the brain tissue was observed as well. Results The brain ATP production in bilirubin induced neurotoxicity guinea pig decreased within 4 hours after exposure to bilirubin, and secondary brain edema could be found 8 hours later; GAPA could prevent the secondary brain edema effectively ,but could not prevent the ATP decreasing significantly. Conclusion NMDA receptor antagonist GAPA could prevent bilirubin induced brain edema, but could not improve the primary brain ATP decrease.更多还原