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经气管内滴注多壁碳纳米管后自发性高血压大鼠的亚慢性毒性及心血管反应

Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation.

作者信息

Chen Rui, Zhang Lili, Ge Cuicui, Tseng Michael T, Bai Ru, Qu Ying, Beer Christiane, Autrup Herman, Chen Chunying

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100090, China.

出版信息

Chem Res Toxicol. 2015 Mar 16;28(3):440-50. doi: 10.1021/tx5004003. Epub 2015 Jan 22.

DOI:10.1021/tx5004003
PMID:25580880
Abstract

The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly.

摘要

市场对碳纳米管的巨大需求导致了其大规模生产,而这通过职业暴露带来了日益增加的风险。已知碳纳米管在肺部沉积会引起急性局部肺部不良反应。然而,与急性肺部病变相关的全身性心血管损害尚未得到充分研究。使用四种不同长度和/或铁含量的多壁碳纳米管(MWCNT),通过气管内滴注法,探讨其对自发性高血压(SH)大鼠和正常血压对照Wistar-Kyoto(WKY)大鼠的潜在亚慢性毒理学效应。MWCNT穿透肺气血屏障并在肝脏、肾脏和脾脏中蓄积,但未在SH大鼠的心脏和主动脉中蓄积。在暴露后7天和30天评估肺部毒性和心血管效应。通过心电图监测发现,与WKY大鼠相比,SH大鼠的血压受到短暂影响,心率持续下降长达30天。在SH和WKY大鼠模型中,暴露后7天和30天均显示出亚慢性毒性,尤其是肺部和心血管系统的持续炎症。组织病理学结果显示,暴露30天后SH大鼠的腹主动脉出现明显的形态学病变。我们的结果表明,应更加关注MWCNT的长期毒性作用,特别是对于已有心血管疾病的职业暴露工人,应进行更全面的监测。

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