支气管喷入高剂量贫铀染毒犬模型早期损伤特点研究

Features of early injuries in canine model of high dose depleted uranium exposure through bronchial spraying

目的探索经支气管喷入高剂量贫铀混悬液染毒早期对机体的损伤特点。方法高剂量贫铀(20 mg/kg)经支气管喷入染毒,建立急性肺损伤染毒犬模型。于沾染前,沾染后3、8 h和1、2、3、5、7 d行血铀含量、动脉血气、血常规、肝功能、肾功能、心肌酶谱、细胞因子等检测及胸部CT检查。结果染毒犬沾染后各时相点血铀含量均高于沾染前(P<0.05),且沾染后8 h和1、2、3、5、7 d低于沾染后3 h(P<0.01),沾染后8 h和7 d高于沾染后1、2、3、5 d(P<0.05);与沾染前相比,白细胞、中性粒细胞计数于沾染后8 h、5 d升高(P<0.05);CK、CK-MB、AST于沾染后3 h升高(P<0.05),肌酐于沾染后5、7 d升高(P<0.01);IL-8于沾染后3、5 d升高(P<0.05)。沾染后各时相点肺部阴影得分均高于沾染前(P<0.01),且沾染后3、8 h得分与其他时相点相比差异均有统计学意义(P<0.01),沾染后1 d得分高于沾染后5、7 d(P<0.05)。结论高剂量贫铀经支气管喷入染毒下,其在机体内的分布速率可能符合二房室模型;沾染后8 h肺部出现严重炎症反应;沾染后5 d肾功能明显受损,且血铀含量随之复升。

Objective To explore the features of early damages due to high dose depleted uranium(DU) exposure through bronchial spraying. Methods A canine model of acute lung injury was established by bronchial spraying of 20 mg/kg DU suspension. Serum uranium content, arterial blood gas, blood routine, liver function, kidney function, myocardial enzymes, cytokines, and CT examination were tested or performed at pre-exposure, and 3 and 8 h and 1, 2, 3, 5 and 7 d after exposure. Results The serum uranium content was significantly increased at all the time points after exposure than the content before exposure(P<0.05). And the content at 8 h and 1, 2, 3, 5 and 7 d was notably higher than the content at 3 h(P<0.01), and that at 8 h and 7 d was obviously higher than it at 1, 2, 3 and 5 d(P<0.05). Compared with the values before exposure, the counts of leukocytes and neutrophils were risen at 8 h and 5 d after exposure(P<0.05), the levels of creatine kinase(CK), creatine kinase-MB(CK-MB) and aspartate aminotransferase(AST) were increased sharply at 3 h(P<0.05), the creatinine level was dramatically elevated at 5 and 7 d(P<0.01), and the level of IL-8 was raised at 3 and 5 d after DU exposure(P<0.05). The CT scanning results showed that the scores of pulmonary shadows were higher at all time points after than before exposure, and there were significant differences in the score at 3 and 8 h when compared with other time points(P<0.01). The score at 1 d was much higher than that at 5 and 7 d(P<0.05). Conclusions The distributing rate of high dose DU exposure through bronchial spraying is possibly in line with two-compartment model. Severe inflammation occurs in the lungs at the 8 th hour after exposure. Renal function is obviously impaired at day 5, along with another rise of serum uranium content.