盐酸氨溴索与柠檬酸廓清肺内难溶性贫铀的实验研究

Clearance of insoluble depleted uranium particles in lungs by citric acid and ambroxol

目的通过建立大鼠贫铀(depleted uranium,DU)气溶胶气管灌注的实验模型,观察柠檬酸雾化吸入与盐酸氨溴索对肺内难溶性贫铀的廓清作用。方法雄性Wistar大鼠150只(体质量200±10 g),随机分为正常对照组(NC组)、贫铀气溶胶染毒组(DU组)、DU+雾化吸入柠檬酸组(CA组)、DU+盐酸氨溴索灌胃组(AM组)、DU+柠檬酸与盐酸氨溴索联用药组(CA+AM组),分别在染毒后7、15、30 d活杀。微波消解法检测肺铀含量,观察肺组织病理改变,检测肺匀浆液炎性因子。结果与DU组相比,给药组在各时间点均明显减少肺内铀的沉积量(P<0.01),CA+AM组肺铀含量低于单独用药组。肺组织病理HE染色显示,染毒后7、15、30 d,治疗组大鼠肺病变明显改善。肺匀浆液炎性因子检测显示,染毒后30 d,与DU组相比,治疗组IL-1α、IL-1β、IL-2水平降低,MCP-1、MIP-1α水平升高。结论使用柠檬酸和盐酸氨溴索均可明显提高肺铀廓清率,联合用药效果优于单独用药,且减轻难溶性铀颗粒对肺组织的破坏。药物治疗可以降低肺内炎性细胞因子水平,对肺部慢性炎症有抑制作用,并且增强巨噬细胞募集能力。

Objective To investigate the effect of citric acid and ambroxol on clearing insoluble particles of depleted uranium in rat lungs by establishing a tracheal perfusion model.Methods One hundred and fifty male Wistar rats were randomly divided into model exposure group, normal control group（NC group）, depleted uranium exposure group（DU）, citric acid treatment group（ CA） , ambroxol treatment group（ AM） and citric acid＋ambroxol treatment group（ CA＋AM） . The rats were sacrificed on 7, 15 and 30 days.Uranium content in the lungs was detected by microwave digestion method, pathological changes in the lungs were observed, and inflammatory factors of lung homogenates were detected.Results Compared to DU control group, the intrapulmonary uranium deposit amount in experimental groups was significantly reduced on 7 and 15 days （P〈0.05）.HE stained lung tissue showed that the pathological changes in treatment groups were less significant than in DU control group.The level of IL-1α,IL-1β,and IL-2 was significantly lower than in DU control, but the level of MCP-1 and MIP-1 was observably higher.Conclusion Citric acid and ambroxol can evidently improve the clear-ance of lung uranium and reduce damnification of lung tissues.Drug treatment can reduce the level of pulmonary inflamma-tory cytokines alleviate the chronic inflammation in the lungs, and enhance the capacity of macrophage to recruitment.