Valentino Sarah A, Chézeau Laëtitia, Seidel Carole, Sébillaud Sylvie, Lorcin Mylène, Chalansonnet Monique, Cosnier Frédéric, Gaté Laurent
Institut National de Recherche et de Sécurité, 1 rue du Morvan, 54510 Vandoeuvre-lès-Nancy, France.
Nanomaterials (Basel). 2021 Jun 1;11(6):1466. doi: 10.3390/nano11061466.
Although aging is associated with a higher risk of developing respiratory pathologies, very few studies have assessed the impact of age on the adverse effects of inhaled nanoparticles. Using conventional and transcriptomic approaches, this study aimed to compare in young (12-13-week-old) and elderly (19-month-old) fisher F344 rats the pulmonary toxicity of an inhaled nanostructured aerosol of titanium dioxide (TiO). Animals were nose-only exposed to this aerosol at a concentration of 10 mg/m for 6 h per day, 5 days per week for 4 weeks. Tissues were collected immediately (D0), and 28 days after exposure (D28). A pulmonary influx of neutrophilic granulocytes was observed in exposed rats at D0, but diminished with time while remaining significant until D28. Similarly, an increased expression of several genes involved in inflammation at the two post-exposure time-points was seen. Apart from an age-specific pulmonary influx of lymphocyte, only slight differences in physio-pathological responses following TiO exposure between young and elderly animals were noticed. Conversely, marked age-related differences in gene expression profiles were observed making possible to establish lists of genes specific to each age group and post-exposure times. These results highlight different signaling pathways that were disrupted in rats according to their age.
尽管衰老与患呼吸道疾病的风险增加有关，但很少有研究评估年龄对吸入纳米颗粒不良反应的影响。本研究采用传统方法和转录组学方法，旨在比较年轻（12 - 13周龄）和老年（19月龄）的Fisher F344大鼠吸入纳米结构二氧化钛（TiO）气溶胶后的肺毒性。动物每天经鼻暴露于该气溶胶，浓度为10 mg/m³，每周5天，每天6小时，持续4周。在暴露即刻（D0）和暴露后28天（D28）采集组织。在D0时，暴露大鼠出现中性粒细胞向肺内浸润，但随着时间推移这种浸润减少，直到D28时仍很显著。同样，在两个暴露后时间点观察到几种参与炎症的基因表达增加。除了淋巴细胞在肺内的年龄特异性浸润外，年轻和老年动物在TiO暴露后的生理病理反应仅存在细微差异。相反，观察到基因表达谱存在明显的年龄相关差异，从而有可能建立每个年龄组和暴露后时间点特有的基因列表。这些结果突出了根据年龄不同而在大鼠体内被破坏的不同信号通路。
