School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Environment and Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Environment and Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Environ Pollut. 2024 Nov 1;360:124580. doi: 10.1016/j.envpol.2024.124580. Epub 2024 Jul 19.
Published evidences have suggested that air pollutant benzo(a)pyrene (BaP) may modify the toxicity and adverse effects produced by other toxicants. However, the precise role of short-term exposure to low-dose BaP on acute lung injury (ALI) induced by crystalline silica (CS) and the underlying mechanisms remain to be clarified. To investigate this issue, a mouse co-exposure model was established by intratracheal instillation of 2.5 mg CS and BaP alone or in combination. Our data found that CS exposure resulted in ALI as evidenced by lung histological changes, elevated lactate dehydrogenase activity, increased level of pro-inflammatory markers and enhanced oxidative damage. Although exposure to BaP alone had little effect on the pathological changes of mice lung tissues except for occasionally mild inflammation, it could aggravate the CS-induced ALI in a dose-dependent manner. Bioinformatic analysis of transcriptome sequencing suggested that the expression changes of significantly differentially expressed genes were closely related to the severity of ALI. The joined analysis of STC and WGCNA found that "NOD-like receptor signaling pathway", "toll-like receptor signaling pathway", "TNF signaling pathway", and "NF-kappa B signaling pathway" associated with immune and inflammatory response were the most prominent significant pathways. TLR2/9 and Nod2 might be the key inflammation-related genes that were differentially expressed in the combined lung toxicity induced by CS and BaP exposure. All these findings suggest that co-exposure of CS and low-dose BaP can cause more severe lung inflammation and oxidative damage in mice than exposure alone, which may be useful in the management and prevention of silicosis. The roles of TLR2/9 and Nod2 as candidate targets in the combined toxicity need further exploration.
已有研究表明，空气污染物苯并(a)芘（BaP）可能会改变其他有毒物质的毒性和不良反应。然而，短期暴露于低剂量 BaP 对二氧化硅（CS）诱导的急性肺损伤（ALI）的影响及其潜在机制仍需阐明。为了研究这个问题，通过气管内滴注 2.5mg CS 和 BaP 单独或联合建立了一个小鼠共暴露模型。我们的数据发现，CS 暴露导致了 ALI，表现为肺组织学变化、乳酸脱氢酶活性升高、促炎标志物水平升高和氧化损伤增强。尽管单独暴露于 BaP 除偶尔轻度炎症外，对小鼠肺组织的病理变化几乎没有影响，但它可以以剂量依赖的方式加重 CS 诱导的 ALI。转录组测序的生物信息学分析表明，差异表达基因的表达变化与 ALI 的严重程度密切相关。STC 和 WGCNA 的联合分析发现，“NOD 样受体信号通路”、“ toll 样受体信号通路”、“TNF 信号通路”和“NF-kappa B 信号通路”与免疫和炎症反应相关，是最显著的显著通路。TLR2/9 和 Nod2 可能是 CS 和 BaP 联合暴露诱导的肺毒性中差异表达的关键炎症相关基因。所有这些发现表明，CS 和低剂量 BaP 的共暴露会导致小鼠肺部炎症和氧化损伤比单独暴露更严重，这可能有助于矽肺的管理和预防。TLR2/9 和 Nod2 作为联合毒性的候选靶点的作用需要进一步探索。
