目的:我们进行了吸入和气管内滴注研究,以检查三氧化钨(WO3)纳米颗粒对肺的影响,并评估纳米颗粒是否会引起持续的肺部炎症。
方法:在吸入研究中,将雄性10周龄Fischer334大鼠分为3组。控制,低剂量,高剂量组吸入清洁空气,2,和10mg/m3的WO3纳米颗粒,分别,每天6小时,共4周。大鼠在3天解剖,1个月,吸入后3个月,并检查支气管肺泡灌洗液(BALF)和肺组织。在气管内滴注研究中,将雄性12周龄Fischer334大鼠分为3个亚组。控制,低剂量,高剂量组气管内滴注0.4ml蒸馏水,0.2和1.0mgWO3纳米颗粒,分别,溶于0.4毫升蒸馏水。3天处死大鼠,1周,气管内滴注后1个月,BALF和肺组织如吸入研究一样进行分析。
结果:吸入和滴注WO3纳米颗粒导致中性粒细胞数量和速率的短暂增加,BALF中细胞因子诱导的中性粒细胞趋化因子(CINC)-1和CINC-2,但肺组织未见组织病理学改变或血红素加氧酶(HO)-1上调。
结论:我们的结果表明WO3纳米颗粒对肺具有低毒性。根据吸入研究的结果,我们还提出WO3纳米颗粒的未观察到的不良反应水平(NOAEL)为2mg/m3。
OBJECTIVE: We conducted inhalation and intratracheal instillation studies in order to examine the effects of tungsten trioxide (WO3 ) nanoparticles on the lung, and evaluated whether or not the nanoparticles would cause persistent lung inflammation.
METHODS: In the inhalation study, male 10-week-old Fischer 334 rats were classified into 3 groups. The control, low-dose, and high-dose groups inhaled clean air, 2, and 10 mg/m3 WO3 nanoparticles, respectively, for 6 h each day for 4 weeks. The rats were dissected at 3 days, 1 month, and 3 months after the inhalation, and the bronchoalveolar lavage fluid (BALF) and lung tissue were examined. In the intratracheal instillation study, male 12-week-old Fischer 334 rats were divided into 3 subgroups. The control, low-dose, and high-dose groups were intratracheally instilled 0.4 ml distilled water, 0.2, and 1.0 mg WO3 nanoparticles, respectively, dissolved in 0.4 ml distilled water. The rats were sacrificed at 3 days, 1 week, and 1 month after the intratracheal instillation, and the BALF and lung tissue were analyzed as in the inhalation study.
RESULTS: The inhalation and instillation of WO3 nanoparticles caused transient increases in the number and rate of neutrophils, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-2 in BALF, but no histopathological changes or upregulation of heme oxygenase (HO)-1 in the lung tissue.
CONCLUSIONS: Our results suggest that WO3 nanoparticles have low toxicity to the lung. According to the results of the inhalation study, we also propose that the no observed adverse effect level (NOAEL) of WO3 nanoparticles is 2 mg/m3 .