Li Ren, Zheng Bingqing, Zhang Yuqiong, He Lu, Ren Chaomin, Guan Linlin, Yang Huan, Tian Jiayu, Chen Xingyi, Shi Dongxing, Zhao Lifang, Zhang Zhihong
Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, Taiyuan, China.
Front Pharmacol. 2025 Mar 14;16:1566965. doi: 10.3389/fphar.2025.1566965. eCollection 2025.
Phthalates (PAEs) are widely used plasticizers in polyvinyl chloride (PVC) products since the 1930s, and recent research indicates a significant association between exposure to these substances and the development and progression of asthma and chronic obstructive pulmonary disease (COPD). Understanding the underlying mechanisms is crucial due to their public health implications.
In this study, we utilized innovative network toxicology and molecular docking techniques to systematically examine the effects of seven typical phthalates on asthma and COPD. By integrating information from multiple databases, we identified key target genes linked to these compounds and conducted functional enrichment analyses to elucidate their roles in pathological processes.
Our results demonstrate that these phthalates affect the pathogenesis of asthma and COPD by modulating various target genes, including PTGS2, MMP9, and CASP3, which are involved in essential biological pathways such as apoptosis and immune response. Interestingly, certain inflammation-related genes and signaling pathways displayed novel regulatory patterns when exposed to phthalates, revealing new pathological mechanisms. Molecular docking analyses further confirmed stable interactions between phthalates and essential target genes, providing molecular-level insights into their pathogenic mechanisms.
Overall, this study highlights the harmful impacts of these seven phthalates on asthma and COPD, establishing new connections between the compounds and disease-related genes, and emphasizing their relevance as emerging environmental toxins. These findings provide valuable perspectives for risk assessment and public health policy, underscoring the need for stricter regulations and interventions regarding phthalate exposure.
自20世纪30年代以来，邻苯二甲酸酯（PAEs）一直是聚氯乙烯（PVC）产品中广泛使用的增塑剂，最近的研究表明，接触这些物质与哮喘和慢性阻塞性肺疾病（COPD）的发生和发展之间存在显著关联。由于其对公众健康的影响，了解其潜在机制至关重要。
在本研究中，我们利用创新的网络毒理学和分子对接技术，系统地研究了七种典型邻苯二甲酸酯对哮喘和COPD的影响。通过整合多个数据库的信息，我们确定了与这些化合物相关的关键靶基因，并进行了功能富集分析，以阐明它们在病理过程中的作用。
我们的结果表明，这些邻苯二甲酸酯通过调节各种靶基因影响哮喘和COPD的发病机制，这些靶基因包括PTGS2、MMP9和CASP3，它们参与凋亡和免疫反应等重要生物学途径。有趣的是，某些炎症相关基因和信号通路在接触邻苯二甲酸酯时表现出新颖的调控模式，揭示了新的病理机制。分子对接分析进一步证实了邻苯二甲酸酯与关键靶基因之间的稳定相互作用，为其致病机制提供了分子水平的见解。
总体而言，本研究突出了这七种邻苯二甲酸酯对哮喘和COPD的有害影响，建立了这些化合物与疾病相关基因之间的新联系，并强调了它们作为新兴环境毒素的相关性。这些发现为风险评估和公共卫生政策提供了有价值的观点，强调了对邻苯二甲酸酯暴露实施更严格监管和干预措施的必要性。
