乐果90d染毒对大鼠大脑皮质GABA系统的影响  

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

作　　者：班婷婷[1] 吴强恩[1] 姚新民[1] 姜楠[1] 邵春风[1] 顾锡安[1] 常秀丽[1] 吴庆[1] 周志俊[1] 

机构地区：[1]复旦大学公共卫生学院教育部公共卫生安全重点实验室,上海200032

出　　处：《环境与职业医学》2007年第6期588-591,共4页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(编号:30571554)

摘　　要：[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。[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 gavage 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 eontents of GABA in the homogenates of cortex. Radioligand receptor binding assay was employed to investigate the binding capacities of GABAA 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 myelencephalon 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 GABAA 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.

关 键 词：有机磷 乐果 GABA GABAA受体 

分 类 号：TQ456.3[化学工程—农药化工]