兴奋性氨基酸在脊髓继发性损伤中作用机制的研究

A mechanism on effect of excitatory amino acid on spinal cord injury

本实验以Ａｌｌｅｎ法造成脊髓损伤（ＳＣＩ）模型，伤后不同时间分别：（１）取伤段脊髓，采用高效液相色谱法检测脊髓组织谷氨酸（Ｇｌｕ）、天门冬氨酸（Ａｓｐ）的含量变化；（２）给予不同剂量Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体拮抗剂４－（３－磷酸基丙基）－２－哌嗪磷酸（ＣＰＰ），４８ｈ后取伤段脊髓以原子吸收光谱法测定其离子改变及水含量。结果发现ＳＣＩ后１０～３０ｍｉｎＧｌｕ、Ａｓｐ较对照组明显升高，其幅度与ＳＣＩ程度呈正相关；损伤组Ｎａ＋、Ｃａ（２＋）和水含量增多，Ｋ＋、Ｍｇ（２＋）减少，ＣＰＰ处理组各种离子和水的改变则较轻，其效果与给药剂量和时间呈正相关。ＣＰＰ的拮抗作用提示ＳＣＩ时的离子和水含量改变与ＮＭＤＡ的过度激活有关。表明ＳＣＩ后急性期兴奋性氨基酸的过度升高很可能参与了脊髓创伤后的继发性损伤过程。

In the present study,Sprague-Dawley rats were subjected to traumatic spinal cord injury using Allen's method.At different periods posttrauma:(1) Reginal concentrations of excitatory amino acid (EAA) were assessed with high-performance liquid chromatography;(2) Reginal water and ion contents of rat spinal cord tissue were measured with the atomic absorption spectrophotometry after administering intrathecally different dosage of 3-(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP),a specific antagonist of N-methyl-D-aspartate (NMDA) receptor,to rats at 48 h posttrauma.The results showed that the concentrations of glutamate and aspartate were rapidly elevated at 10-30 min after trauma and related to the severity of injury.In the injured segment there was a significant increase in water,Na￣+ and Ca￣(2+) and decrease in K￣+ and Mg￣(2+).Whereas in CPP treatment group they had a statistical significant return,which was related to administered dosage and time.The effects of CPP suggest that ion and water content are related to overactivation of NMDA receptor.Excessive high levels of EAA may be involved in secondary tissue damage after spinal cord injury.