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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 establish an experimental model of aerosol tracheal perfusion in depleted uranium (DU) rats and observe the effect of inhalation of citric acid and ambroxol hydrochloride on the resolution of intra-pulmonary insoluble lean uranium. Methods 150 male Wistar rats (200 ± 10 g body weight) were randomly divided into normal control group (NC group), DU depleted group (DU), DU + nebulized citric acid group (CA group) DU + hydrochloric ambroxol group (AM group), DU + citric acid combined with ambroxol hydrochloride group (CA + AM group) were killed at 7,15,30 d after exposure. The content of uranium in the lungs was detected by microwave digestion, the pathological changes of lung were observed, and the inflammatory cytokines in lung homogenate were detected. Results Compared with the DU group, the administration group significantly reduced the deposition of uranium in the lung (P <0.01) at each time point. The content of uranium in the CA + AM group was lower than that of the DU alone group. HE staining of lung histopathology showed that the lung lesions in the treatment group were significantly improved at 7, 15 and 30 days after exposure. Inflammatory cytokines in lung homogenate showed that the levels of IL-1α, IL-1β, IL-2 and MCP-1 and MIP-1α in the treatment group were significantly lower than those in the DU group at 30 days. Conclusions Both citric acid and ambroxol hydrochloride can significantly improve the clearance rate of uranium, and the combined effect is better than that of single drug and relieve the damage of insoluble uranium particles to lung tissue. Drug treatment can reduce the levels of inflammatory cytokines in the lungs, inhibit chronic lung inflammation, and enhance macrophage recruitment ability.