敌敌畏对大鼠脑组织N-甲基-D-天门冬氨酸受体活性的影响

Effect of DDVP on activity of N-methyl-D-aspartate receptor in brain of rat

目的 研究敌敌畏 (DDVP)染毒后大鼠脑组织中N 甲基 D 天门冬氨酸 (NMDA)受体的变化规律 ,探讨其在有机磷农药中毒中的作用。方法 5 5只雄性SD大鼠分为 11组 ,每组 5只 ,一组为生理盐水 (NS)组 ,高剂量组( 2 5mg/kg)和低剂量组 ( 15mg/kg)各 5组 ,染毒组分别以敌敌畏腹腔注射 ,染毒后 4h、 8h、 16h、 2 4h、 48h处死 ,测定大鼠全血和脑组织的乙酰胆碱酯酶 (AChE)活性以及脑组织中NMDA受体的活性。结果 DDVP染毒后大鼠全血和脑组织的AChE活性显著下降 ,且脑组织AChE活性下降更多 ,抑制率大于 80 % ,恢复更迟缓。脑组织中NMDA受体的最大结合容量 (Bmax)在 4h便明显下降 ,于 2 4h达到最低 ,然后逐渐升高 ,受体的平衡解离常数 (Kd)在 4h时明显上升 ,于 2 4h达到最高 ,然后逐渐下降。结论 DDVP染毒对大鼠脑组织AChE活性抑制严重 ,说明中枢神经系统对DDVP的毒作用敏感。同时DDVP染毒对大鼠脑组织中NMDA受体产生下降调节 ,表现为受体数量减少、亲和力降低。推测这是机体的一种自身调节机制 。

Objective To study the effect of DDVP on the activity of NMDA receptor in brains of male rats,thereby to understand its role played in the pathogenesis of organophosphates poisoning.Method Fifty five male Sprague Dawley rats were randomly divided into 11 groups.Control group was administrated with normal saline by intraperitoneal injection only instead of dichlorvos.The exposed rats were divided into high dose group and low dose group,each had five sub groups;rats of high group were given 25 mg/kg dichlorvos ip,rats of low dose group were given 15 mg/kg dichlorvos ip.Then,to measure the values of AChE and the binding capacity of NMDA receptor at the 4 h,8 h,16 h,24 h and 48 h after injection,respectively.The binding capacity of NMDA receptor was measured withMK 801 and B max and Kd were determined by Scatchard analysis.Result The AChE activities in whole blood and brain of dichlorvos exposed rats were obviously inhibited;especially the latter,which decreased by 80% or more and recovered slowly,too.The B max of NMDA receptor in brain began to decrease at 4 h after injection of dichlorvos and reached its lowest level at 24 h after injection.While the Kd was significantly risen at 4 h after dichlorvos injection and reached its peak by the time of 24 h after dichlorvos injection.Conclusion It was showed that the inhibition of brain AChE activity was more severe than that of whole blood after dichlorvos injection,suggesting that the central nervous system was more sensitive to the acute toxicity of dichlorvos.In addition,dichlorvos might evoke down regulation ofMK 801 binding to NMDA receptor in rat brain which were expressed as significant decrease in quantity and affinity of NMDA receptors,supposing that it may be a self regulation mechanism for protecting central nervous system from dichlorvos intoxication.