College of Engineering, Northeast Agricultural University, Harbin, China.
College of Life Science, Northeast Agricultural University, Harbin, China.
Inhal Toxicol. 2020 Aug;32(9-10):388-401. doi: 10.1080/08958378.2020.1831112. Epub 2020 Oct 12.
The growing applications of nanocelluloses in the fields of advanced nanocomposites, electronics, and medical devices necessitate investigation of their potential adverse effects on human health. The lungs are the primary and the most important route for the entry of nanocelluloses into the human body in occupational settings. However, data on the pulmonary toxicity of cellulose nanofibrils (CNFs) and its molecular mechanism are limited. This study investigated the pulmonary toxicity of CNFs and its genomic expression using the RNA sequencing approach.
Female C57BL/6 mice were administered CNFs at 50 μg/mouse by oropharyngeal aspiration. Samples were collected at 3 and 14 days after exposure to CNFs (DAEC).
At three DAEC, the microscopic sections of lungs revealed a significant inflammatory response. In terms of gene expression alterations, 94 genes were up-regulated, and 107 genes were down-regulated. Most of these differentially expressed genes were involved in the inflammatory and immune responses, including chemokines, NK cells, killer cell lectin-like receptors, CD antigens, T cell-specific GTPases, immunity-related GTPase family M members, and interferon-induced proteins encoding genes. However, only 9 and 26 genes at 14 DAEC were significantly up- and down-regulated, respectively.
The pathological analysis of lung sections and the analysis of sequencing data suggested that the homeostasis of mice lungs was restored at 14 DAEC. The findings of this study provide insights into the pulmonary toxicity, and underlying toxicological mechanisms, caused by exposure to CNFs, and are useful for the assessment of the potential toxicity of nanocelluloses.
纳米纤维素在先进纳米复合材料、电子和医疗器械领域的应用日益广泛,因此有必要研究其对人体健康的潜在不良影响。在职业环境中,纳米纤维素进入人体的主要途径和最重要途径是肺部。然而,关于纤维素纳米纤维(CNF)的肺部毒性及其分子机制的数据有限。本研究采用 RNA 测序方法研究了 CNF 的肺部毒性及其基因组表达。
雌性 C57BL/6 小鼠通过口咽吸入给予 CNFs,剂量为 50μg/只。在暴露于 CNFs 后 3 天和 14 天(DAEC)收集样本。
在 3 DAEC,肺的显微镜切片显示出明显的炎症反应。在基因表达改变方面,有 94 个基因上调,107 个基因下调。这些差异表达基因大多与炎症和免疫反应有关,包括趋化因子、NK 细胞、杀伤细胞凝集素样受体、CD 抗原、T 细胞特异性 GTPase、免疫相关 GTPase 家族 M 成员和干扰素诱导蛋白编码基因。然而,在 14 DAEC 时,仅有 9 个和 26 个基因分别显著上调和下调。
肺组织切片的病理分析和测序数据的分析表明,在 14 DAEC 时,小鼠肺部的内稳态得到了恢复。本研究结果为暴露于 CNF 引起的肺部毒性及其潜在毒理学机制提供了新的认识,有助于评估纳米纤维素的潜在毒性。