肺部吸入微球致大鼠急性肺损伤的初步研究

Acute Lung Injury Induced by Inhalable Microparticles in Rats

目的对吸入微球的肺部安全性进行初步研究。方法通过考察肺组织的病理变化、肺泡灌洗液成分分析评估微球的初步安全性,探讨微球致肺损伤的机制。结果经肺给予微球后可引起肺部的病理损伤,并表现出剂量依赖性。与正常大鼠相比,给药组肺泡灌洗液中各成分均有所升高。病理表现为以细支气管为中心的炎症反应,粒细胞浸润,毛细血管扩张充血、通透性增加,肺间质水肿以及肺上皮细胞损伤。结论吸入微球可致大鼠肺损伤,应对该给药系统的安全性给予高度关注,建立完善的评价体系。

OBJECTIVE To investigate the safety of inhalable microparticles in rats. METHODS The safety of the microparti- cles was assessed by lung histology and analysis of the components in bronchoalveolar lavage fluid. RESULTS The microparticles could induce acute lung injury in rats after inhalation, which showed dose dependency. Compared with the normal group, the concen- trations of biochemical indicators in bronchoalveolar lavage fluid were increased, and pathological changes of lung tissues were observed after intrapulmonary delivery of the microparticles. CONCLUSION Inhalable microparticles can induce acute lung injury in rats. More work should be done to establish systemic assessment for this drug delivery system.