多壁碳纳米管致大鼠肺损伤效应的研究

The Study of Pulmonary Toxicity of Multi-wall Carbon Nanotubes in Rats

[目的]探讨多壁碳纳米管(multi-wall carbon nanotubes,MWCNTs)对大鼠的肺损伤效应。[方法]Wistar大鼠160只,随机分成5组:生理盐水对照组、脱氧核苷酸钠盐(deoxyribonucleic acid sodium salt,DNA钠盐)组、DNA钠盐-MWCNTs 2.0、10.0、20.0mg/mL3组(低、中、高染毒组),并用DNA钠盐提高MWCNTs的分散度。采用气管滴注的方法染毒,一次滴注量为每kg体重1.5mL,每天1次,连续滴注3d,分别于滴注结束后24h、7d、28d、90d时间段,每实验组各处死8只动物,测定肺灌洗液中总蛋白(TP)、乳酸脱氢酶(LDH)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)等细胞毒性及细胞氧化损伤指标及大鼠体重,并观察动物肺组织病理学改变情况。[结果]MWCNTs染毒结束后24h,各染毒组大鼠进食及饮水量均有所下降。染毒结束后7、28、90d时,大鼠体重与滴注前体重相比有不同程度的升高,但染毒剂量越高,体重增加幅度越小。中、高剂量染毒组灌洗液中TP和LDH含量随着染毒浓度的增加而升高;灌洗液中GSH和SOD有不同程度的下降,但随时间的延长有不同程度的升高。电镜下,MWCNTs染毒后7d可观察到大鼠肺组织细胞核膜发生肿胀,核固缩,单位膜结构不清楚;内质网扩张,线粒体发生肿胀,嵴断裂等病理改变。[结论]MWCNTs可引起肺组织损伤和氧化损伤,对大鼠具有肺毒性作用。

[ Objective] To study the pulmonary toxicity of the multi-wall carbon nanotubes in rat.[ Methods] 160 Wistar rats divided into 5 groups at random and exposed to blank control, solvent control and different doses of MWCNTs（2.0, 10.0, 20.0 mg/mL）by intra-tracheal instillation once a day for 3 continuous days respectively. Rats were necrospied at 24 h, 7 d, 28 d and 90 d afterexposure. The weight of rats was weighed. The broncho-alveolar lavage fluid（BALF）was collected and analyzed; and pulmonary morphological change was observed under electron microscope. Indicators of cytotoxicity and oxidative stress, including TP, LDH, GSH and SOD in BALF were measured.[ Results] Results showed that the intake of water and food were decreased sharply after intratracheal instillation, especially at 24 h. The changes of weight were convalescent with time, which accord to the different doses of MWCNTs. The levels of TP and LDH in BALF were raised, while GSH and SOD levels were lowered than control significantly. The oxidative stress response and cytotoxicity tended to recover with time, too. Nucleus membrane damage, nuclear pyknosis, ring-shaped mitochondria, break of crest, and swelling of endoplasmic reticulum were found in MWCNTs-treated group. [Conclusion] MWCNTs induces pulmonary toxicity in rat.