猪百草枯急性中毒灌胃模型的建立与研究  

Establishment and study of a swine gavage model of acute paraquat poisoning

作　　者：邢晶晶 孙昊 张劲松 马天龙 黄培培 蒋云飞 黄翔 王军 XING Jingjing SUN Hao ZHANG Jinsong MA Tianlong HUANG Peipei JIANG Yunfei HUANG Xiang WANG Jun(Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical Universi ty,Nanjing 210029 ,China)

机构地区：[1]南京医科大学第一附属医院急诊医学科,南京210029

出　　处：《临床急诊杂志》2017年第9期677-681,共5页Journal of Clinical Emergency

基　　金：国家自然科学基金(No:81571875;81671899);江苏省科技厅重点病种规范化诊疗研究(No:BL2014088)

摘　　要：目的:建立更接近和符合百草枯中毒临床实际情况的家猪百草枯急性中毒灌胃模型,以满足针对洗胃、血液灌流等治疗开展疗效观察的模型需求。方法:小型雌性家猪镇静麻醉、气管插管及心电监护后,分别以生理盐水(对照组)、30mg/kg、60mg/kg、120mg/kg(百草枯染毒组)的剂量经胃管给予浓度为40%的百草枯原液。持续监测生命体征,留取0、2、4、6、8、12、24h,血浆标本采用液相色谱质谱连用法检测血浆百草枯浓度,留取给药前和给药后24h血液标本送检血气分析、血常规、肝肾功能及电解质,于24h处死、收获动物并留取组织样本。结果:预实验发现百草枯30mg/kg染毒剂量下,2周内动物无明显的脏器功能损伤;120mg/kg染毒剂量下,动物在12h内因循环衰竭而死亡。百草枯60mg/kg剂量组染毒后,与对照组相比动物在24h存活率为66.67%,血药浓度提示灌胃模型的血浆百草枯峰浓度为(5.12±2.38)μg/ml,染毒组的生命体征、肝肾功能电解质、乳酸水平等与对照组相比均差异有统计学意义,氧分压在24h有下降趋势但差异无统计学意义。60mg/kg染毒组动物组织病理检查发现,肺组织急性炎症明显,肺泡腔内大量中性粒细胞及炎性渗出,肾小管上皮细胞水肿,部分坏死。结论:小型家猪可应用于百草枯急性中毒的灌胃模型。适合实验的百草枯染毒剂量是60mg/kg。Objective：To establish a swine gavage model of acute paraquat poisoning which is more common and consistent with the actual clinical situation. Such animal model may meet the needs of gastric lavage,hemoperfusion and other treatment study in the future. Method： Female domestic swine were sedated; endotracheal intubation and ECG monitoring were applied. Saline or different doses （30 mg/kg, 60 mg/kg, 120 mg/kg） of 40% concentration paraquat solution was infused by intragastrie administration. Vital signs were continuous monitored for 24 hours. Plasma samples were collected at every 2 hours until H8,and then at H12 and H24,and paraquat concentration were measured by Liquid chromatography-tandem mass spectrometry. On H0 and H24, blood samples were obtained for blood gas analysis, blood routine examination, liver and kidney function and electrolyte analysis. Animals were harvested at H24 ,and tissues were used for histological analysis. Result：Compared with control group, swine ingested paraquat at dose of 30 mg/kg, demonstrated no difference in vital signs, blood routine examination results, liver and kidney function, electrolyte, blood gas analysis results, etc. Animal model did not show clinical acute paraquat poisoning signs. The swine ingested paraquat at dose of 120 mg/kg,animal models demonstrated decrease in blood pressures within 12 hours, accelerated heart rate and other failures in systematic circulating func- tions which died immediately ~ The survival rate of 60 mg/kg group was 66.67 % （4/6）within 24 hours, plasma con- centration indicated the peak time of paraquat level within gastric lavage model was around 8 hours. The vital signs,liver and kidney function, electrolyte serum lactate levels within paraquat groups illustrated significant differ ence with control group,partial pressure of oxygen indicated a decreasing trend within 24 hours but have no significant difference. Under histopathology examination, pulmonary alveolus and interstitial congestion, cellular infiltration signs were alr

关 键 词：百草枯 动物模型 急性中毒 灌胃 

分 类 号：R595.4[医药卫生—内科学]