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[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 study the effects of 90 [d, O-dimethyl-S- (N-methylcarbamoylmethyl) disulfide phosphate) on the γ- aminobutyric acid (GABA) system in rat cerebral cortex Impact. [Methods] Forty-eight healthy male Sprague-Dawley rats were divided into 4 groups at doses of O (normal saline), 5, 10, and 20 mg / kg orally. The rats were orally administered 5 days a week for 90 days. The animals were weighed once, the consumption of animal feed was recorded every 3 days, and the activity of acetylcholinesterase (AChE) in the whole blood was measured regularly. All the animals were sacrificed by decapitation at the end of the experiment. AChE activity in medulla oblongata was measured. The brain was determined by reversed-phase high performance liquid chromatography Cortical GABA content, radioligand receptor binding assay of the cerebral cortex GABA_A receptor activity. [Result] During the experiment, the activity of AChE in whole blood of all the exposed groups was obviously inhibited, and recovered in the later stage of the experiment. At the end of the experiment, AChE activities in medulla oblongata of low, middle and high exposure groups were about 78%, 63% and 42% of those in control group respectively. Compared with the control group, the levels of GABA in the middle and high dose groups were significantly decreased (P <0.01); the maximum binding capacity (Gmax) of the GABA_A receptor was increased in the low dose group (P <0.05) (P <0.05). The equilibrium dissociation constant (Kd) of GABA_A receptor in each dose group was lower than that in control group, but there was significant difference between low dose and middle dose groups (P <0.05) . [Conclusion] GABA content and GABA_A receptor function of cerebral cortex in dimethoate during90d exposure may be changed, which may be involved in the non-cholinergic mechanism of dimethoate poisoning.