补骨脂素通过调节微生物群依赖性色氨酸代谢改善脓毒症诱导的急性肺损伤
Psoralen ameliorates sepsis-induced acute lung injury by regulating microbiota-dependent tryptophan metabolism.
摘要(中文译文)
脓毒症常导致急性肺损伤（ALI）。尽管补骨脂素（PSO）的抗炎作用已有文献记载，但其对脓毒性ALI发挥保护作用的确切机制仍知之甚少。本研究探讨了PSO在脓毒症诱导的ALI中的保护效果及机制。采用脂多糖（LPS）建立小鼠ALI模型，评估病理及炎症反应。通过肠道菌群清除和粪菌移植评估其对肠道菌群的依赖性。通过AhR激动剂FICZ和拮抗剂CH-223191验证芳香烃受体（AhR）的参与。在脓毒性ALI模型中，PSO改善了组织病理学损伤并减轻了炎症反应。证据包括肺部中性粒细胞比例降低，促炎介质肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β以及MPO-DNA复合物含量减少。此外，PSO下调了肺组织中关键标志物的丰度，包括肽酰精氨酸脱亚氨酶4、集落刺激因子2、瓜氨酸化组蛋白H3和MPO，从而抑制中性粒细胞胞外诱捕网的形成。此外，PSO改变了肠道微生物多样性，该效应依赖于源自肠道菌群的色氨酸代谢。该处理提高了血清中吲哚-3-丙酸（IPA）的相对丰度，随后激活AhR/CYP1A1通路，从而减轻ALI。此外，PSO增强了肠道紧密连接蛋白的表达。然而，这些保护作用被AhR抑制剂CH-223191所消除。
Abstract
Sepsis frequently leads to acute lung injury (ALI). Despite the documented anti-inflammatory effects of Psoralen (PSO), the exact mechanism by which it confers protection against septic ALI remains poorly understood. This research explored the protective efficacy and mechanistic aspects of PSO in sepsis-induced ALI. Lipopolysaccharide (LPS) was employed to create a murine ALI model. Pathological and inflammatory responses were evaluated. The dependency on gut microbiota was assessed through intestinal flora ablation and fecal microbiota transplantation. The aryl hydrocarbon receptor (AhR) engagement was demonstrated by its agonist FICZ and antagonist CH-223191. In a septic ALI model, PSO ameliorated the histopathological damage and attenuated the inflammatory response. Evidence for this included a lower lung neutrophil percentage and decreased amounts of the proinflammatory mediators tumor necrosis factor-α, interleukin-6, interleukin-1β, as well as MPO-DNA complexes. Additionally, PSO downregulated the abundance of key markers in pulmonary tissue, including peptidylarginine deiminase 4, colony-stimulating factor 2, citrullinated histone H3, and MPO, thereby suppressing neutrophil extracellular trap formation. Furthermore, PSO altered gut microbial diversity, an effect that relied on tryptophan metabolism originating from the gut microbiota. The treatment raised the relative abundance of indole-3-propionic acid (IPA) in serum, which subsequently triggered the AhR/CYP1A1 pathway and thereby alleviated ALI. Moreover, PSO enhanced intestinal tight junction protein expression. Nonetheless, these protective effects were abolished by the AhR inhibitor CH-223191.
如何引用
AMA
Yunqi Kong, Jieni Feng, Haoxiang Xu, Xueru Chen, Wanhua Huo, Simin Pan, et al. Psoralen ameliorates sepsis-induced acute lung injury by regulating microbiota-dependent tryptophan metabolism.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158396.
APA
Yunqi Kong, Jieni Feng, Haoxiang Xu, Xueru Chen, Wanhua Huo, Simin Pan, et al (2026). Psoralen ameliorates sepsis-induced acute lung injury by regulating microbiota-dependent tryptophan metabolism.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158396
GB/T 7714
Yunqi Kong, Jieni Feng, Haoxiang Xu, Xueru Chen, Wanhua Huo, Simin Pan, et al. Psoralen ameliorates sepsis-induced acute lung injury by regulating microbiota-dependent tryptophan metabolism.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158396.
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