不同暴露剂量急性敌草快中毒大鼠毒代动力学及胃肠损伤的实验研究  

Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses

作　　者：张建爽 孙艺青 高恒波[1] 苑霖 姚冬奇[1] 刘亮[1] 吕宝谱 田英平[1] Zhang Jianshuang;Sun Yiqing;Gao Hengbo;Yuan Lin;Yao Dongqi;Liu Liang;Lyu Baopu;Tian Yingping(Department of Emergency Medicine,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei,China)

机构地区：[1]河北医科大学第二医院急诊科,石家庄050000

出　　处：《中华危重病急救医学》2023年第6期651-657,共7页Chinese Critical Care Medicine

基　　金：河北省自然科学基金(H2019206317)。

摘　　要：目的观察不同染毒剂量敌草快(DQ)中毒大鼠毒代动力学特点、胃肠道不同部位吸收特征及病理形态损害。方法将96只健康雄性Wistar大鼠按随机数字表法分为对照组(6只)和低剂量(115.5 mg/kg)、中剂量(231.0 mg/kg)、高剂量(346.5 mg/kg)DQ染毒组(各剂量组30只),各剂量染毒组再随机分为染毒后15 min和1、3、12、36 h 5个亚组(各亚组6只)。各剂量染毒组均给予一次性DQ灌胃染毒;对照组给予等量生理盐水灌胃。记录大鼠的一般情况,各亚组大鼠分别选3个时间点行眼内眦采血,并于第3次取血后处死留取胃肠标本。采用超高效液相色谱-质谱联用仪测定血浆及组织中DQ浓度,绘制血药浓度-时间曲线,计算毒代动力学参数;光镜下观察肠道形态结构,测定绒毛高度和隐窝深度并计算两者比值(V/C)。结果低、中、高剂量染毒组大鼠染毒后5 min即可在血浆中检测到DQ,DQ达血浆峰浓度时间(Tmax)分别为(0.85±0.22)、(0.75±0.25)、(0.25±0.00)h,3个剂量组血浆DQ浓度随时间变化的趋势相似,但高剂量组在36 h时血浆DQ浓度又有所上升。胃肠组织DQ浓度方面,各剂量染毒组大鼠在染毒后15 min~1 h胃和各段小肠DQ浓度最高,3 h时结肠浓度最高;至染毒后36 h,低、中剂量组胃肠各部位DQ浓度已下降至较低水平;高剂量组胃肠组织(除空肠外)DQ浓度较12 h均有升高趋势,仍可检测出较高剂量的DQ〔胃、十二指肠、回肠、结肠DQ浓度分别为6400.0(1232.5)、4889.0(6070.5)、10300.0(3565.0)、1835.0(202.5)mg/kg〕。光镜下观察肠道形态学和组织病理学变化显示,各剂量DQ染毒后15 min,大鼠胃、十二指肠、空肠即出现急性损伤表现,回肠和结肠在染毒后1 h出现病理损伤,12 h时胃肠损伤最重,各段小肠的绒毛高度显著降低、隐窝深度显著增大、V/C比值降至最低,至染毒后36 h损伤开始减轻;同时,随染毒剂量增加,大鼠各时间点的肠道形态学和组织病理学�Objective To observe the toxicokinetic parameters,absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat(DQ).Methods Ninety-six healthy male Wistar rats were randomly divided into a control group(six rats)and low(115.5 mg/kg),medium(231.0 mg/kg)and high(346.5 mg/kg)dose DQ poisoning groups(thirty rats in each dose group),and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure(15 minutes and 1,3,12,36 hours;six rats in each subgroup).All rats in the exposure groups were given a single dose of DQ by gavage.Rats in the control group was given the same amount of saline by gavage.The general condition of the rats was recorded.Blood was collected from the inner canthus of the eye at 3 time points in each subgroup,and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens.DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry(UPHLC-MS),and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters;the morphological structure of the intestine was observed under light microscopy,and the villi height and crypt depth were determined and the ratio(V/C)was calculated.Results DQ was detected in the plasma of the rats in the low,medium and high dose groups 5 minutes after exposure.The time to maximum plasma concentration(Tmax)was(0.85±0.22),(0.75±0.25)and(0.25±0.00)hours,respectively.The trend of plasma DQ concentration over time was similar in the three dose groups,but the plasma DQ concentration increased again at 36 hours in the high dose group.In terms of DQ concentration in gastrointestinal tissues,the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours.By 36 hours after poisoning,the concentrations of DQ in all parts of the stomach and intestine in the low and

关 键 词：敌草快 毒代动力学 胃肠道 

分 类 号：R595.4[医药卫生—内科学]