Zhou Yu Qing, Peng Jin Jin, Shan Li Ping, Liu Wei
Emergency Department, The First Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China.
Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Respir Res. 2025 Jan 2;26(1):1. doi: 10.1186/s12931-024-03072-x.
We sought to explore the molecular mechanisms underpinning acute lung injury (ALI) caused by poisoning with paraquat (PQ).
Selection mice were intraperitoneally injected with PQ at 40 mg/kg, whereas controls were injected with sterile saline. On days 2, 7, and 14 after administration, mice were anesthetized and sacrificed, and lung tissue was removed. Lung pathological changes were observed with conventional staining techniques. Lung tissue components were assessed with tandem mass spectrometry tag technology, and differentially expressed proteins (DEPs) were bioinformatically analyzed and investigated with parallel reaction monitoring.
The expression of 91, 160, and 78 proteins was significantly altered at days 2, 7, and 14, respectively. Gene Ontology analyses revealed that the DEPs in the PQ-2d and PQ-7d groups were involved primarily in humoral immunity and coagulation-related reactions, whereas those in the PQ-14d group were implicated primarily in chemotactic and regulatory responses. Kyoto Encyclopedia of Genes and Genomes analyses indicated that complement and coagulation cascades were key pathways in the PQ-2d and PQ-7d groups, whereas xenobiotic metabolism by cytochrome P450 was a key pathway in the PQ-14d group. Nine proteins at PQ-2d and eight proteins at PQ-7d were validated through parallel reaction monitoring (PRM).
PQ-induced ALI depends on over-activation of immune responses by damaged alveolar/endothelial cells, and the complement/coagulation cascade pathway plays a key role during this process. The proteins identified herein might provide new therapeutic targets or biomarkers for PQ poisoning.
我们试图探究百草枯（PQ）中毒所致急性肺损伤（ALI）的分子机制。
选择小鼠腹腔注射40mg/kg的PQ，而对照组注射无菌生理盐水。给药后第2、7和14天，将小鼠麻醉并处死，取出肺组织。用传统染色技术观察肺组织病理变化。用串联质谱标签技术评估肺组织成分，对差异表达蛋白（DEPs）进行生物信息学分析，并通过平行反应监测进行研究。
分别在第2、7和14天，91、160和78种蛋白质的表达发生了显著变化。基因本体分析显示，PQ - 2d组和PQ - 7d组中的DEPs主要参与体液免疫和凝血相关反应，而PQ - 14d组中的DEPs主要参与趋化和调节反应。京都基因与基因组百科全书分析表明，补体和凝血级联反应是PQ - 2d组和PQ - 7d组中的关键途径，而细胞色素P450介导的异源物质代谢是PQ - 14d组中的关键途径。通过平行反应监测（PRM）验证了PQ - 2d组中的9种蛋白质和PQ - 7d组中的8种蛋白质。
PQ诱导的ALI依赖于受损肺泡/内皮细胞对免疫反应的过度激活，补体/凝血级联途径在此过程中起关键作用。本文鉴定的蛋白质可能为PQ中毒提供新的治疗靶点或生物标志物。
