乐果90 d染毒对大鼠大脑皮质GABA系统的影响

[目的]研究乐果[O,O-二甲基-S-(N-甲基氨基甲酰甲基)二硫化磷酸酯]90d染毒对大鼠大脑皮质γ-氨基丁酸(GABA)系统的影响。[方法]48只健康雄性SD大鼠分成4组,剂量分别为O(生理盐水)、5、10、20mg/kg,灌胃给药,每周染毒5d(次),实验周期90d,每天称重1次,每3天记录动物饲料消耗量,定期测定全血乙酰胆碱酯酶(AChE)活性,实验结束时全部动物断头处死,测定延髓AChE活性,反相高效液相色谱荧光法测定大脑皮质GABA含量,放射性配体受体结合法测定大脑皮质GABA_A受体的活性。[结果]实验期间,各染毒组动物全血AChE活性明显抑制,实验后期有所恢复。实验结束时,低、中、高染毒组延髓AChE活性分别约为对照组的78%、63%、42%。与对照组相比,中、高剂量组大脑皮质GABA含量明显降低(P<0.01);GABA_A受体的最大结合容量(maximum binding capacity,Bmax)低剂量组升高(P<0.05),中剂量组降低(P<0.05);各剂量组GABA_A受体的平衡解离常数(equilibrium dissociation constant,Kd)比对照组均有降低,但仅低、中剂量组差异有统计学意义(P<0.05)。[结论]乐果90d染毒过程中大脑皮质GABA含量、GABA_A受体功能都有所改变,可能参与了乐果慢性中毒过程中的非胆碱能机制。

Changes of GABAergic System in Cerebral Cortex of Rats Treated with Dimethoate for 90 d

[Objective]To explore the effects of dimethoate on GABAergic system in the cerebral cortex of rats exposed to dimethoate for 90 days.[Methods]Dimethoate at the doses of 0(saline vehicle),5,10 and 20mg/kg was administered via garage to rats 5 times a week for 90 days.Both the body weights and food consumption of the rats were recorded.Additionally,the activities of acetylcholinesterase (AChE) in whole blood were determined with UV spectrophotometry regularly during the experimental period.Rats were decapitated at the end of the study and the isocratic reversed high-performance liquid chromatography system with fluorescence detection(HPLC-FLD)was applied to measure the contents of GABA in the homogenates of cortex.Radioligand receptor binding assay was employed to investigate the binding capacities of GABA_A receptor.[Results]The activities of whole blood AChEs decreased significantly during the experimental period (P<0.01).Similarly,significant depression of AChEs was observed in rat myeleneephalon as compared with the control group at the end of the test(P<0.01).Levels of GABA in the cerebral cortex decreased significantly at the dose of 10,20 mg/kg bw comparing to the control group (P<0.01).The densities (Bmax values)of cerebral cortex GABA_A receptor were significantly higher than the controls at the dose of 5 mg/kg bw(P<0.05) but lower at 10mg/kg bw(P<0.05).Anyway,Kd values were lower at both doses of 5 and 10mg/kg bw(P<0.05).[Conclusion] The GABAergic system in rat cerebral cortex was involved in the rat chronic dimethoate intoxication and it play an important role in the organophosphates non-cholinergic mechanisms.