家兔经口染毒百草枯的毒效动力学研究  

Study on toxicodynamics of paraquat administered by gavage in rabbits

作　　者：郭伟 张艳芳 郭翔 李培茂 张志敏 杨祥丽 汤海燕 GUO Wei;ZHANG Yanfang;GUO Xiang;LI Peimao;Zhang Zhimin;YANG Xiangli;TANG Haiyan(The First Affiliated Hospital of Nanchang University,Nanchang,Jiangxi 330000,China;Shenzhen Prevention and Treatment Center for Occupational Disease,Shenzhen,Guangdong 518020,China)

机构地区：[1]南昌大学第一附属医院,江西南昌330000 [2]深圳市职业病防治院,广东深圳518020

出　　处：《职业卫生与应急救援》2021年第5期509-513,548,共6页Occupational Health and Emergency Rescue

基　　金：广东省医学科研基金(A2021417);深圳市职业病防治院科研培育计划项目(KPⅡ-202001)。

摘　　要：目的探讨家兔经口染毒百草枯的毒物效应动力学规律。方法20只家兔随机分为3组。对照组(6只):以2 mL/kg体质量的生理盐水灌胃;低剂量染毒组(6只):以100 mg/kg体质量的百草枯溶液灌胃;高剂量染毒组(8只):以200 mg/kg体质量的百草枯溶液灌胃。各组家兔分别在染毒前和染毒后8 h、24 h、72 h及7 d采集外周血用于生化指标、细胞因子和血气分析指标的检测;染毒后7 d,取动物肺组织进行病理学观察。结果高剂量染毒组有2只家兔分别于染毒后30 h和75 h死亡(不纳入统计)。染毒动物在观察期的体质量增加量低于对照组(P<0.05),高、低剂量染毒组之间体质量差异无统计学意义(P>0.05),染毒7 d后,各组血清谷丙转氨酶、谷草转氨酶、肌酸激酶同工酶、乳酸脱氢酶、α-羟丁酸脱氢酶、尿素、肌酐、总蛋白、白蛋白水平和动脉血气分析结果差异无统计学意义(P>0.05)。染毒7 d后,各组血清转化生长因子β_(1)(transforming growth factor-β_(1),TGF-β_(1))水平均升高(P<0.05),高剂量组升高幅度更大;高剂量组高迁移率族蛋白B1(HMGB1)水平高于对照组和低剂量组(P<0.05)。百草枯可致急性肺损伤和早期肺纤维化等病理组织学改变。结论经口染毒百草枯可导致生长受限,部分炎症因子水平增加,还可引起肺组织损伤。研究结果可为研究百草枯中毒救治措施的动物实验提供基础数据,为百草枯中毒患者预后判断提供参考。Objective To understand the toxicodynamics of paraquat in rabbits.Methods A total of 20 rabbits were randomly divided into three groups,namely control group(n=6)dosed with 2 mL/kg normal saline by gavage,low dose group(n=6)dosed with 100 mg/kg paraquat,and high dose group(n=8)dosed with 200 mg/kg paraquat.Serum biochemical indexes,cytokines and arterial blood gas were analyzed before dosing and 8 h,24 h,72 h,7 d after administration.Histopathology of lung were implemented after 7 days of exposure.Results In the high dose group,2 rabbits were died at 35 h and 75 h,respectively(the following data were not included these 2 rabbits).The increase of body mass of the poisoned animals during the observation period was lower than that of the control group(P<0.05),and there was no significant difference in body mass between two dosed groups(P>0.05).After 7 days of exposure,there was no significant difference of serum alanine aminotransferase,aspartate aminotransferase,creatine kinase isozyme,lactate dehydrogenase,α-hydroxybutyrate dehydrogenase,urea,creatinine,total protein,albumin and arterial blood gas analysis(P>0.05).After 7 days of exposure,the levels of serum transforming growth factor β_(1)(TGF-β_(1))in the three groups were increased(P<0.05),especially in the high dose group.The level of high mobility group protein B1(HMGB1)in high dose group was higher than that in control group and low dose group(P<0.05).Histopathological examination showed paraquat caused acute lung injury and early pulmonary fibrosis.Conclusions Paraquat poisoning can cause growth restriction,increase levels of some inflammatory factors and cause lung damage.These results can provide a reference for the prognosis of patients with paraquat poisoning,and provide basic data for other animal experiments.

关 键 词：百草枯 毒物效应动力学 纤维化 家兔 转化生长因子 

分 类 号：R99[医药卫生—毒理学]