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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 model of acute poisoning of paraquat in domestic pigs that is closer to and in line with the clinical situation of paraquat poisoning to meet the needs of model for the observation of curative effects such as gastric lavage and hemoperfusion. Methods: Small female domestic pigs were anesthetized by sedation, tracheal intubation and electrocardiogram (ECG) monitoring. After intravenous injection of saline (control group), 30mg / kg, 60mg / kg and 120mg / Give paraquat stock solution at a concentration of 40%. Continuous monitoring of vital signs, 0,2,4,6,8,12,24 h, plasma samples using liquid chromatography mass spectrometry for the detection of plasma paraquat concentration, 24h before administration and after administration of blood samples for inspection Blood gas analysis, blood, liver and kidney function and electrolytes were sacrificed at 24 h, animals were harvested and tissue samples were taken. Results: The pre-experiment showed that the paraquat 30mg / kg dose, 2 weeks of animals without significant organ damage; 120mg / kg dose, the animals died within 12h due to circulatory failure. After being exposed to 60mg / kg paraquat, the survival rate of the animals at 24h was 66.67% compared with that of the control group. The plasma concentration of paraquat showed a peak plasma concentration of (5.12 ± 2.38) μg / ml, There were significant differences in the vital signs, electrolyte of liver and kidney electrolytes, lactate levels compared with the control group. The oxygen partial pressure decreased at 24h, but the difference was not statistically significant. The histopathological examination of 60mg / kg group showed that the acute inflammation of lung tissue was obvious, a large number of neutrophils and inflammatory exudation in alveolar cavity, tubular epithelial cell edema and partial necrosis. Conclusion: Small domestic pigs can be used in gavage model of acute paraquat poisoning. The paraquat dose suitable for the experiment is 60 mg / kg.