静脉注射多壁碳纳米管对高脂饮食大鼠肺组织的毒性

Pulmonary toxicity in high-fat diet SD rats induced by intravenous injection of multi-walled carbon nanotubes

目的探讨静脉注射多壁碳纳米管（MWCNTs）对高脂饮食SD大鼠肺组织的毒性。方法将140只雄性sD大鼠随机分成正常对照组、高脂对照组、溶剂对照组、低剂量组（各30只），中、高剂量组（各10只）。正常对照组给予正常饲料，其余各组在染毒前以70万U／kg维生素D3灌胃3d后予高脂饮食。溶剂组予含1％tween80的生理盐水（0．2ml／100g）尾静脉注射，每周2次；低剂量组予MWCNTs50p,g／kg尾静脉注射，每周2次，分别于8、12、16周后处死。中、高剂量组予MWCNTs100、200μg／kg尾静脉注射，每周2次，于16周后处死。计算大鼠各组肺脏系数，对肺组织行HE染色，光学显微镜下观察肺组织病理学改变。荧光定量实时PCR检测肺组织匀浆中白细胞介素1β（IL-1β）和肿瘤坏死因子（TNF—α）mRNA表达水平。结果与溶剂对照组相比，中、高剂量组肺脏系数均明显增加，差异有统计学意义（P〈0．05）。染毒16周后，HE染色可见低、中、高3个剂量组出现不同程度肺部黑色颗粒积聚，伴有肺出血、纤维化和肉芽肿形成。与溶剂对照组比较，染毒12周低剂量组及染毒16周低、中、高3个剂量组肺组织中IL-1βmRNA表达水平均明显降低，差异有统计学意义（P〈0．05）。与溶剂对照组比较，染毒8、16周低剂量组肺组织中TNF—αmRNA表达水平明显升高，染毒12周低剂量组和染毒16周中、高剂量组肺组织中TNF-仪mRNA表达水平明显降低，差异均有统计学意义（P〈0．05）。结论静脉注射MWCNTs可引起大鼠肺部纳米材料积聚，并出现慢性炎症性病理改变。

Objective To observe the pulmonary toxicity of muhi-walled carbon nanotubes （MWC- NTs） in high-fat diet SD rats. Methods One hundred forty male SD rats were randomly divided into 6 groups. The normal control group, high-fat diet model group, vehicle group, and group treated with low dose of MWCNTs consisted of 30 rats, respectively, which were divided in 3 subgroups （ 10 rats each subgroup）, respectively. The groups treated with medium and high loses of MWCNTs consisted of 10 rats, respectively. All the animals were exposed to high-fat-diet except for the control group which was given with normal diet. Before intravenous exposure, the high-fat diet model group, vehicle group, and three MWCNTs treated groups were gavaged with 700 thousand U/kg Vit D3 for three days, then given with high-fat-diet. The vehicle group was exposed to normal saline containing 1% Tween 80 and the low exposure group was exposed to MWCNTs at the dose of 50μg/kg by tail vein injection twice a week for 8, 12 or 16 weeks. Other tow exposure groups were exposed to MWCNTs at the doses of 100, and 200 μg/kg by tail vein injection twice a week, respectively for16 weeks. The lungs were from the executed rats, the lung indexes were calculated, the pathological changes of lungs were examined under light microscope after HE staining, qRT-PCR assay was utilized to detect the expression levels of pro-inflammation cytokines IL-1β（IL-1β） and TNF-α mRNA in the lungs. Results As compared with the vehicle group, the lung indexes in groups exposed to 100 and 200 μg/kg MWCNTs increased significantly （P〈0.05）. It was found under light microscope that the MWCNTs were accumulated in lungs of three exposure groups in 16 weeks after exposure, including pneumorrhagia, alveolar walls thicken, fibrosis, and granulomas. As compared with the vehicle group, the levels of IL-1β mRNA in group exposed to 50 μg/kg MWCNTs for 12 weeks and the groups exposed to 50, 100 and 200 μg/kg MWCNTs for 16 weeks decreased significantly （P〈0.05）. As compared with the vehicle group, the levels of TNF-α mRNA in the groups exposed to 50 μg/kg MWCNTs for 8 and 16 weeks in creased significantly （P〈0.05）, the level of TNF-α mRNA in the groups exposed to 50 μg/kg MWCNTs for 12 weeks decreased significantly （P〈0.05）. As compared with the vehicle group, the level of TNF-α mRNA in the groups exposed to 200 Ixg/kg MWCNTs for 16 weeks reduced significantly （P〈0.05）. Conclusion The MWCNTs accumulation and chronic iuflamnmtory changes were found in the lungs of rats exposed to MWCNTs by tail vein injection.