谷氨酸诱导大鼠海马脑片Ca^（2＋）／CaM　PK　Ⅱ活性的抑制作用

THE INHIBITION OF Ca￣(2+)/CaM PK Ⅱ ACTIVITY INDUCED BY GLUTAMATE IN RAT HIPPOCAMPAL SLICES

目的研究外源性谷氨酸对海马脑片Ｃａ２＋／ＣａＭＰＫⅡ活性的影响及氯胺酮的保护作用，同时研究缺氧对神经元外谷氨酸堆积的影响。方法采用体外培养的大鼠海马脑片研究这些作用。结果（１）海马脑片在体外缺氧３０ｍｉｎ，谷氨酸在胞外的堆积增加２倍多；（２）单纯过量外源性谷氨酸能引起酶活性显著下降，仅为对照组的２４％，提示脑缺氧时酶活性的抑制与兴奋毒性有关；（３）氯胺酮对单纯外源性谷氨酸所诱导的酶活性抑制有明显的拮抗作用，说明脑缺氧引起酶活性下降与ＮＭＤＡ受体介导有关。结论脑缺氧时该酶活性的抑制与下列通路有关：谷氨酸→ＮＭＤＡ受体→Ｃａ２＋→Ｃａ２＋靶酶。

Objective: To examine the effects of glutamate and ketamine on Ca2+/CaM PK Ⅱ activity and the effect of hypoxia on glutamate accumulation. Method: Using the rat hippocampal slice as a model for investigating these effects. Results: (1) The extracelluar accumulation of glutamate increased about two folds after hypoxia for 30 min in vitro. (2) When the slices were incubated for 30 min under conditions in excess of exogenous glutamate alone, the enzyme activity decreased to only 24% the control value, suggesting that the inhibition of enzyme activity induced by brain hypoxia may result from excitotoxicity. (3) The inhibition of enzyme activity induced by excessive exogenous glutamate could be antagonized markedly by pretreatment with ketamine, showing that the hypoxia-induced inhivition of the enzyme activity in the brain is mediated by NMDA receptor. Conclution:The brain hypoxia-induced inhibition of the enzyme activity is mediated by the following pathway: glutamate→NMDA receptor→Ca￣2+→Ca￣2+ target enzyme.