贫铀吸入性肺损伤犬模型的建立

摘要

Objective To reproduce a canine model of subacute lung injury induced by depleted uranium inhalation.Methods Twenty-six dogs were randomized into the control group (CG, n=6), low-dose group (LG, n=10).and high-dose group (HG, n=10).All of them underwent tracheal intubation.In control group, 0.2ml/kg of normal saline was intratracbeally given.In low dosage group, 10mg/kg of depleted uranium (LG),and in high dose group 100mg/ml of depleted uranium (HG) was introduced.The survival time of animals was observed in one month after intratracheal introduction of various agents, and chest CT scan was performed in the survived animals.They were sacrificed for pathological examination of lung tissues on the 31st day post of them intratracheal introduction of various agents.Results During the observation period, no animal died in CG, one dog in LG died on the 22nd day and 9 of them survived longer than 30 days.All the animals in HG group died within 30 days with a mean survival time of 11.2 ±8.9 days (median= 12d).In comparison with the HG, significant difference on survival time was found between LG and CG, while no significant difference was found between the latter 2 groups (P=0.439).Pathologically, changes were noted in lung tissue of LG, such as escape of inflammatory cells into alveoli, hemorrhage and hyaline membrane formation in alveolar space, dilatation and congestion of alveolar capillaries, and infiltration of inflammatory cells in interstitial tissue.CT scanning revealed patchy effusion and solid consolidation in the left lung.Conclusion The canine model of subacute lung injury induced by a dose of 2mg/kg depleted uraniun introduced through tracheal intubation is suitable for the study of subacute toxicity induced by depleted uranium.%目的 建立适用于亚急性贫铀吸入性肺损伤研究的犬模型.方法 将26只犬随机分为对照组(n=6)、低剂量组(n=10)和高剂量组(n=10).3组犬麻醉后经气管插管,行左侧肺灌注,对照组给予0.2ml/kg生理盐水,低、高剂量组分别给予低浓度(10mg/ml)和高浓度(100mg/ml)贫铀混悬液.记录贫铀灌注后各组犬的生存时间,观察时间截止为贫铀灌注后30d.在灌注后31d,对存活犬行胸部CT检查,处死后取肺组织行病理检查.结果 在30d的观察期内,对照组动物无死亡,低剂量组中1只犬在贫铀灌注后22d死亡,其余犬存活均超过30d;高剂量组所有犬均在30d内死亡,存活时间11.2±8.9(中位值12)d.高剂量组与低剂量组和对照组比较,差异有统计学意义(P=0.000),但后两组比较差异无统计学意义(P=0.439).低剂量组肺组织的病理学改变主要为肺泡腔内炎细胞渗出、出血及透明膜形成,肺泡壁毛细血管扩张、充血,肺间质炎细胞浸润;胸部CT显示左肺片状渗出和实变影.结论 采用贫铀混悬液以2mg/kg剂量行单侧肺灌注所建立的犬模型,适合用于进行1个月内亚急性贫铀毒性的实验研究.