| 肟硫磷的毒物代谢动力学和毒效学 |
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| 引用本文： | 顾兵,王心如,何凤生. 肟硫磷的毒物代谢动力学和毒效学[J]. 中国药理学与毒理学杂志, 2000, 14(5): 364-368 |
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| 作者姓名： | 顾兵 王心如 何凤生 |
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| 作者单位： | 南京医科大学公共卫生学院!江苏南京210029(顾兵，王心如)，中国预防医学科学院劳动卫生与职业病研究所!北京100050(何凤生) |
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| 基金项目： | 国家“九五”科技攻关项目!(96 - 90 6 - 0 4- 11)，江苏省卫生厅科技发展项目!(H97- 16 ) |
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| 摘 要： | 采用高效液相色谱法 ,测定血清和脑组织匀浆中的肟硫磷 ,揭示其经口染毒 SD大鼠体内的毒物代谢动力学过程 ;以血清丁酰胆碱酯酶 (BCh E)和脑组织乙酰胆碱酯酶 (ACh E)的抑制率及一氧化氮合酶 (NOS)活性为毒效应指标 ,阐明肟硫磷的毒效动力学特征 .给大鼠 ig肟硫磷 2 75mg·kg-1后 ,血清毒物浓度 -时间曲线符合一级吸收一室开放模型 ,ka= 1 .87h-1,Tp=1 .2 6h,Cmax=1 .90 mg· L-1.ACh E抑制效应与血清肟硫磷浓度之间呈逆时针滞后环 .脑组织中 NOS活性随时间进程的异常波动 ,提示 NO参与产生非胆碱能神经毒作用 . BCh E抑制以后不能迅速自动恢复 ,所致酶的“老化”,可能是产生胆碱能效应的直接证据
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| 关 键 词： | 肟硫磷 色谱法,高效液相 毒物代谢动力学 毒效学 乙酰胆碱酯酶 丁酰胆碱酯酶 一氧化氮合酶 |
| 收稿时间： | 2000-01-13 |
Toxicokinetics and toxicodynamics of phoxim in rats |
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| GU Bing, WANG Xin-Ru, HE Feng-Sheng. Toxicokinetics and toxicodynamics of phoxim in rats[J]. Chinese Journal of Pharmacology and Toxicology, 2000, 14(5): 364-368 |
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| Authors: | GU Bing WANG Xin-Ru HE Feng-Sheng |
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| Affiliation: | GU Bing1, WANG Xin-Ru1, HE Feng-Sheng2 |
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| Abstract: | The biological samples were extracted with ethylacetate and concentrated. Employing the high performance liquid chromatography with a reverse phase chromatographic column of Lichrosorb Si 60 and a mobile phase of tetrahydrofuran/petroleum ether (1.4/98.6) for determination of phoxim content in serum and brain homogenate, the toxicokinetic profile of phoxim administrated orally in rats was illustrated. Meanwhile, using the inhibition rate of serum butyrylcholinesterase (BChE) activity and brain homogenate acetylcholinesterase (AChE) activity as well as the activity of nitric oxide synthase (NOS) in brain homogenate as toxic effect indices, its toxicodynamics was explored. Toxicokinetic studies of phoxim in rat after 275 mg·kg-1 intragastic administration demonstrated that serum phoxim concentration against me profile was fitted well to the one-compartment open model with 1st order absorption. Toxicokinetic parameters and their values calculated from this model were ka 1.87 h-1, t1/2 (ka) 0.37 h，Tp 1.26 h, Cmax 1.90 mg·L-1. Relationship between inhibitory effect on AChE and serum phoxim concentration was indicated as a counterclock-wise hysteresis loop. The abnormal fluctuation of NOS activity in brain, with the time prolonging, indicated that NO involved in the non-cholinergic neurotoxicity. These results, rather slower auto-reactivation and aging of inhibited BChE, may suggest pronounced evidence for its role in cholinergic effect. |
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| Keywords: | phoxim chromatography high performance liquid toxicokinetics toxico- dynamics acetylcholinesterase butyryl- cholinesterase nitric oxide synthase |
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