纳米SiO2与标准SiO2对大鼠肺毒作用的比较研究

Study of toxicity to rats induced by nanosized SiO2 and standard SiO2

目的 观察纳米SiO2与标准SiO2对大鼠的肺部毒性作用。方法 72只雄性SD大鼠分为纳米SiO2组、标准SiO2组和对照组，每组24只。纳米SiO2组或标准SiO2组分别一次性气管注入纳米SiO2或标准SiO2颗粒悬浮液0．5ml，分别观察3、7、14、28d后，各处死6只大鼠，测定肺泡灌洗液（BALF）中的白细胞总数和总蛋白含量；HE染色和胶原纤维（VG）染色进行病理观察。结果 染尘3、7、14d纳米SiO2组大鼠BALF中自细胞总数[（16．0±6．0）×10^6、（11．1±4．0）×10^6、（12．2±4．6）×10^6]明显高于对照组，差异有统计学意义（P〈0．05或P〈0．01），纳米SiO2染尘3d时明显高于标准SiO2组[（5．7±3．7）×10^6]，差异有统计学意义（P〈0．01）。染尘14、28d纳米SiO2组大鼠BALF中总蛋白含量[（0．41±0．14、0．41±0．19）g／L]明显高于对照组和标准SiO2组相应时间点的总蛋白含量，高于纳米SiO2染尘3和7d时的总蛋白含量，差异均有统计学意义（P〈0．05或P〈0．01）。染尘3d时，纳米SiO2组肺泡腔、支气管壁及血管壁周白细胞严重浸润，标准SiO2组肺泡腔及血管壁周也有炎性浸润，但比纳米SiO2组轻。两组VG染色均未见明显胶原纤维分布。结论 在该实验条件下，纳米SiO2引起大鼠早期肺部炎症反应比标准SiO2严重，持续时间更长，引起肺部损害的颗粒负荷阈值可能比标准SiO2低。

Objective To study the pulmonary toxicity to rats induced by the nanosized SiO2 or the standard SiO2. Methods Seventy-two male SD rats were divided into three groups： the nanosized SiO2 group, the standard SiO2 group and the control group, 24 rats each group. The nanosized SiO2 group and the standard SiO2 group were instilled intratracheally with 0.5 ml suspension of 0.6 mg/ml nanosized SiO2 and standard SiO2 respectively while the control group was instilled with 0.5 ml physiological saline. On the 3rd, 7th, 14th and 28th day after exposure, six rats were sacrificed at each time point and the total white cells counts and total protein in BALF and the histopathological changes were observed, The pulmonary toxicities of the two SiO2 dusts were compared. Results Nanosized SiO2 caused significant increase on the 3rd, 7th, 14th day after the exposure [ （ 16.0±6.0）×10^6, （ 11. 1±4.0）×10^6, （12.2±4.6）×10^6] compared with saline （P〈0.05 or P〈0.01） in the total numbers of white cells and on the 3rd day after the exposure compared with standard SiO2 [ （5.7±3.7）×10^6, P〈0.01 ]. Meanwhile, nanosized SiO2 significantly increased the total protein on the 14th, 28th day after the exposure （0.41±0.14, 0.41±0.19 g/L） compared with the saline or standard SiO2 and nanosized SiO2 on the 3rd, 7th day after the exposure（P〈0.05 or P〈0.0 1）. Nanosized SiO2 treated rats showed marked white cell infiltration in the alveolar space or around brondus the blood vessel. Standard SiO2 caused similar but less severe responses compared with nanosized SiO2. Van Gieson＇ s-stained sections showed no significant fibrosis in these dust-exposed rats on the 28th day after the exposure. Conclusion Nanosized SiO2 can cause severer and longer pulmonary toxicity in rats than standard SiO2. The pulmonary particle load threshold ofnanosized SiO2 may be lower than that of standard SiO2.