兔急性灭多威中毒毒代动力学观察  

Toxicokinetics of methomyl in rabbits

作　　者：王志翊[1] 汪春龙 王贤亲[3] 陈进[1] 孙来芳[1] 马建设[2] 

机构地区：[1]温州医科大学附属第二医院急诊科,浙江温州325027 [2]温州医科大学基础学院,浙江温州325035 [3]温州医科大学分析测试中心,浙江温州325035

出　　处：《温州医学院学报》2015年第7期469-473,共5页Journal of Wenzhou Medical College

基　　金：国家自然科学基金资助项目(81401558);浙江省自然科学基金资助项目(LY14H230001);浙江省卫生厅科研基金资助项目(2014KYA 144);温州市公益性科技计划项目(Y20140493)

摘　　要：目的:观察兔急性灭多威中毒的毒代动力学,探讨其对组织器官的损害作用。方法:一次性予灭多威剂量12 mg/kg灌胃染毒,观察其不同时间点的症状与体征;采用液相色谱-质谱/质谱联用(LC-MS/MS)技术检测兔血浆中灭多威吸收、代谢过程,并绘制浓度-时间曲线;用DAS 2.0软件分析并计算毒代动力学参数;荧光倒置显微镜观察兔脑、心、肝、肾脏器病理学改变;生化仪分析各时间点的血生化指标。结果:灭多威毒代动力学参数分别为AUC0-t(1 209.734±219.542)μg/h·L、MRT0-t(1.731±0.144)h、t1/2z(1.471±0.277)h、Tmax 0.25 h、CLz/F(9.576±1.816)L·h-1·kg-1和Vz/F(20.225±4.703)L/kg;光镜下观察,心肌、肝、脑组织均可见充血、水肿、细胞浸润等病理学改变。谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)在染毒后6 h时升高,与染毒前相比差异有统计学意义(P<0.05);肌钙蛋白-I(c Tn-I)在染毒后2 h时升高,与染毒前相比差异有统计学意义(P<0.05);胆碱酯酶(Ach E)活性在染毒后0.25 h迅速降低,与染毒前相比差异有统计学意义(P<0.05),6 h后恢复至正常水平。结论:灭多威灌胃染毒后的毒物代谢动力学符合二室模型,其体内半衰期短,中毒后代谢迅速,对脑、心、肝、肾等脏器均有不同程度损害作用。Objective： To observe the toxicokinetics of acute methomyl poisoning in rabbits, and to explore its damaging effects on tissue and organ.Methods： Disposable gavageing methomyl dose 12 mg/kg, to observed symptoms and signs at different time points. The process of metabolism and absorption of methomyl were de-tected by Liquid chromatography-mass spectrometry/mass spectrometry in rabbit plasma, drawing concentration-time curve. The toxicokinetic parameters were analyzed and calculated by DAS 2.0 software. The pathological changes of brain, heart, liver, kidney were observed under inverted lfuorescence microscope. Blood biochemistry was analyzed with biochemical analyzer at each time point.Results： The parameters were AUC0-t（1 209.734± 219.542）μg/L＆#183;h. MRT0-t（1.731±0.144） h, t1/2z （1.471±0.277） h, Tmax 0.25 h, CLz/F （9.576±1.816） L＆#183;h-1＆#183;kg-1, Vz/F （20.225±4.703） L/kg in methomyl toxicokinetics. The pathological changes, cellular inifltration and edema were visible under light microscope in heart, liver, brain. Compared with previous exposure, the Alanine amino-transferase （ALT）, aspartate aminotransferase （AST）, lactate dehydrogenase （LDH）, creatine kinase （CK） elevated after exposure for 6 h, the differences were statistically signiifcant （P〈0.05）. Troponin-I （cTn-I） increased at 2 h after exposure, the differences were statistically signiifcant （P〈0.05）. Cholinesterase （AchE） activity decreased rapidly after 0.25 h exposure, the differences were statistically signiifcant （P〈0.05）, returned to normal levels after exposure for 6 h.Conclusion： The toxicokinetics of Methomyl gavaged poison is in accordance with two-compartment model, its half-life in vivo is short, metabolism is rapid after poisoning, different degrees damages are detected in the brain, heart, liver, kidney organs.

关 键 词：灭多威 毒物代谢动力学 液相色谱质谱联用 病理学改变 兔 

分 类 号：R994.1[医药卫生—毒理学]