目的探讨连续动式吸入条件下不同浓度的纳米二氧化硅(SiO:)是否可以导致大鼠肺部明显的毒性作用。方法48只雄性sD大鼠按体重随机分成4组,包括分散剂对照组(对照组,生理盐水)和纳米SiO2低剂量组(质量浓度为O.3%)、中剂量组(质量浓度为1.0%)和高剂量组(质量浓度为3.0%)。于动式染毒28d后(每天染毒2h)处死动物,采集肺泡灌洗液(BALF)和肺组织,观察肺脏器系数、BALF中白细胞总数及分类、总蛋白含量、乳酸脱氢酶(LDH)活力、肺组织病理改变(HE染色)和怖纤维化形成情况(VG染色)。结果与对照组相比,纳米SiO,组肺脏器系数的差异无统计学意义(p〉0.05)。1.0%和3.0%纳米SiO2组BALF中的白细胞总数明显高于对照组,差异有统计学意义(P〈O.05)。各剂量纳米SiO2组的总蛋白含量和LDH活力与对照组比较,差异均无统计学意义(P〉0.05)。与对照组相比,各剂量纳米SiO2组淋巴细胞的比例明显降低,单核和巨噬细胞的比例明显升高,差异有统计学意义(P〈0.05)。HE染色显示,纳米SiO2组肺泡壁明显增厚,支气管和血管壁周围发生明显的炎性细胞浸润,各纳米SiO2组肺纤维化VG染色均未见胶原纤维分布的明显增加。结论本实验条件下,连续28d动式吸人纳米SiO2只引起大鼠肺部显著的炎症反应,未出现肺纤维化现象。
Objective To investigate the puhnonary toxicity of different concentrations of nano-silica (nano-SiO2) under continuous dynamic inhalation conditions in the rat. Methods 48 male Sprague-Dawley rats were randomly divided into four groups, including the dispersant control group (saline) and nano-SiO2 low dose group (0.3%, w/v), the middle-dose group (1%) and the high-dose group (3%). Animals were sacrificed at 28 d after exposure under continuous dynamic inhalation conditions, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. And following items were observed: body coefficient, BALF related items (leukocytes and classification, total protein content, LDH activity), lung tissue pathological changes (HE staining),andpulmonaccfibrosisforming (collagenfiberVGstaining).Results Comparedtothedispersanteontrol group, there was no significant change on lung organ coefficient in Nano-SiO2 group (PM3.05). The BALF total WBC count in 1% and 3% in nano-SiO2 groups showed higher value than the dispersant control group (P〈0.05). No obvious changes were found on total protein content and LDH activity in nano-SiO2 groups compared to the dispersant control group (P〉0.05). For differential WBC counts, lymphocyte count in BALF in nano-SiO2 groups was significantly decreased (P〈0.05), monocyte and macrophage counts were significantly increased (P〈O.05), but there was no difference on the proportion of neutrophils (P〉O.05). HE staining results showed that the obvious thickening of alveolar wall in nano-SiO2 groups, inflammatory cell infiltration also increased around the bronchial and vascular wall. Lung fibrosis VG staining showed no significant change of collagen fiber distribution. Conclusion Under our experimental conditions, the continuous dynamic inhalation of nano-SiOz only caused the significant inflammation in rat lungs, pulmonary fibrosis phenomenon could not be observed significantly.