来亨鸡迟发性神经毒性模型的建立及对95%嘧啶氧磷原药迟发性神经毒性的评价  

Establishment of the model of delayed neurotoxicity with Leghorn chicken and assessment of the delayed neurotoxicity of 95% pyrimyxthion

作　　者：刘英华[1] 姜淑卿[1] 周庆红[1] 李树飞[1] 张静[1] 张力[1] 张书婧[1] 钱智勇[1] LIU Yinghua;JIANG Shuqing;ZHOU Qinghong;LI Shufei;ZHANG Jing;ZHANG Li;ZHANG Shujing;QIAN Zhiyong(Tianjin Centers for Disease Control and Prevention,Tianjin 300011,China)

机构地区：[1]天津市疾病预防控制中心

出　　处：《公共卫生与预防医学》2019年第3期48-52,共5页Journal of Public Health and Preventive Medicine

摘　　要：目的建立鸡迟发性神经毒性模型,并对95%嘧啶氧磷原药的迟发性神经毒性进行评价。方法研究利用来亨鸡进行试验,试验设三邻甲苯磷酸酯(Tri-o-cresyl phosphate,TOCP)组(500mg/kg·BW)、溶剂对照组、95%嘧啶氧磷原药低、中、高剂量组(53.8mg/kg·BW、107.5mg/kg·BW、215.0mg/kg·BW),每组15只,一次给药后观察临床症状及组织病理学改变,并进行生化指标神经病靶酯酶(neuropathy target esterase,NTE)和乙酰胆碱酯酶(acetylcholin esterase,ACHE)的测定。结果TOCP组于给药第10d起相继出现明显迟发性神经毒性反应。病理组织学检查可见脱髓鞘病变。TOCP染毒24h和48h对脑和腰部脊髓中NTE抑制率>70%,ACHE活力低于溶剂对照组(P<0.01),NTE活力48h后与24h后活力无明显差异;48h后ACHE活力比24h后活力降低。1周后NTE和AChE活力均呈现恢复趋势。溶剂对照组及95%嘧啶氧磷原药各剂量组均未见明显相关反应。结论NTE可作为迟发性神经毒早期诊断的指标,ACHE活力随时间的变化趋势也可以做为早期预测和诊断OPIDN发生的重要指标。95%嘧啶氧磷原药未见迟发性神经毒性。Objective To establish the chicken model of delayed neurotoxicity and test the delayed neurotoxicity of 95% pyrimidinoxy phosphorus. Methods Leghorn chicken was used in the present study. The chickens were divided into 5 groups,including tri-o-tolyl phosphate (TOCP) group (500 mg/kg BW),solvent control group,95% pyrimyxthion groups (53.8,107.5,and 215.0 mg/kg BW,respectively),with 15 chickens in each group. Clinical symptoms and pathological changes were observed after one administration of the chemicals,and the determination of neuropathy target esterase (NTE) and acetylcholine esterase (ACHE) was performed. Results Ten days after administration,the TOCP group showed significant delayed neurotoxicity,and demyelination were observed in histopathological examination. The inhibition rate of NTE in brain and lumbar spinal cord was >70% in relative to the solvent control after TOCP exposure for 24h and 48h,and the ACHE activity was lower than that of the control group ( P <0.01). There was no significant difference in NTE activity after 48h compared to that after 24h. After 48h,ACHE activity decreased compared to that after 24h. Both NTE and AChE activities were elevated after 1 week. There was no significant correlation between the solvent control group and the 95% pyrimyxthion group. Conclusion NTE can be used as an early diagnosis of delayed neurotoxicity. The change of AChE activity over time can also be used as an important indicator for early prediction and diagnosis of OPIDN. 95% pyrimidinyl phosphate drug has no late neurotoxicity .

关 键 词：迟发性神经毒性 神经病靶酯酶 乙酰胆碱酯酶 95%嘧啶氧磷 

分 类 号：R114[医药卫生—卫生毒理学] R994.6[医药卫生—公共卫生与预防医学]