乐果急性染毒对大鼠海马抑制性氨基酸神经递质的影响

Acute effects of dimethoate on inhibitory amino acid neurotransmitters in rat hippocampus

目的研究乐果急性染毒对大鼠海马抑制性氨基酸γ-氨基丁酸(GABA)和甘氨酸(Gly)含量的影响以及它们的剂量-时程-效应关系。方法大鼠38.9、83.7、180mg/kg乐果腹腔注射后于0.5、2、8、24h断头取海马,对照组注射生理盐水。Asch-DTNB法测定全血及海马中乙酰胆碱酯酶活性,高效液相色谱荧光法测定海马匀浆液中GABA、Gly的含量。结果全血及海马中胆碱酯酶活性显著下降,同对照相比,各剂量组各时间段全血AChE活性均低于50%,海马低于75%,存在剂量依赖性并在24h后活性有所恢复。海马GABA及Gly含量都有不同程度增加,其中海马低剂量组各时间段,中剂量组0.5、2、8h,高剂量组0.5、24h GABA含量与对照组相比都有统计学差异。Gly低剂量组在染毒8h,中剂量组0.5h,高剂量组0.5、24h的含量可见有统计学差异的升高。结论乐果急性染毒后,大鼠海马抑制性氨基酸GABA及Gly有代偿性升高,GABA存在剂量-时程-效应关系,Gly存在时程-效应关系,同传统的有机磷胆碱能中毒机制一起,发挥乐果的毒作用。

Purpose This study aimed to explore the dose-time-effect relationships of numerous inhibitory amino acid neurotransmitters, including ）＇-aminobutyric acid（GABA） and Glycine（Gly） in the hippocampus of dimethoate-treated rats. Methods The treated rats were decapitated at the selected time points of 0. 5, 2, 8 and 24 h after the administration of dimethoate at the dose of 38.9, 83.7 and !80 mg/kg intraperitoneally respectively, and the controls received the equal volume of saline vehicle. The activities of acetylcholinesterase（AChE） in whole blood and hippocampus were determined with UV spectrophotometry. The isocratic reversed high-performance liquid chromatography system with fluorescence detection（HPLC-FL） was applied to measure the contents of GABA and Gly in the homogenates of hippocampus. Results Both blood and hippocampus AChEs depressed significantly and recovered slightly 24 h after the treatment. The concentrations of GABA and Gly in hippocampus showed a general and gradual elevation after the administration. Levels of GABA were significantly increased in the hippocampus at all selected time points at the dose of 38.9 mg/kg; at 0. 5, 2, 8 h and at 0. 5 h, 24 h at the dose of 83.7 mg/kg and 180.0 mg/kg respectively. Conclusions The CNS inhibitory amino acid transmitters system including GABA and Gly was involved in the rat acute dimethoate intoxication and it may play an important role in the organophosphates non-cholinergic mechanisms.