简介：脓毒症是一种临床综合征，其特征是感染导致宿主免疫反应失调，导致危及生命的器官损伤。尽管积极推广和实施早期预防措施和集束治疗，脓毒症仍然表现出高发病率和死亡率，并且没有最佳的药物干预措施。 Lobetyolin (LBT) 是党参中发现的聚乙炔的关键成分，已被科学证明具有有效的抗氧化和抗肿瘤特性。然而，其治疗脓毒症的潜力仍然未知。方法：小鼠腹腔注射LBT进行预处理，随后注射脂多糖（LPS）诱导脓毒症。采集外周血样本检测TNF-α、IL-1β、IL-6水平。在不同的时间间隔记录不同组的生存状态。 RNA-Seq 用于分析经 LBT 或 LPS 处理的腹膜巨噬细胞的基因表达。结果：在本研究中，我们观察到在 LPS 诱导的脓毒症小鼠模型中，经 LBT 预处理的小鼠的存活率显着增加。 LBT 显着减少了血清中 IL-6、TNF-α 和 IL-1β 的产生，并减轻了肺和肝组织损伤，其特征是炎症细胞浸润减少。此外，通过RNA-seq分析结合GO和KEGG分析，发现LBT有效抑制与细菌存在、细胞对脂多糖刺激的反应以及涉及Cxcl10、Tgtp1、Gbp5、Tnf、 Il1b 和 IRF7 特别位于巨噬细胞内。我们还证实，LBT 显着下调 LPS 诱导的巨噬细胞活化中 IL-6、TNF-α 和 IL-1β 的表达。讨论：因此，我们的研究结果表明，LBT 可有效抑制炎症细胞因子（IL-6、TNF-α 和 IL-1β）的产生，并通过调节巨噬细胞产生这些细胞因子的能力来减轻 LPS 诱导的脓毒症。这些结果表明，LBT 有希望成为脓毒症治疗的潜在治疗剂。版权所有 © 2024 Chen、Su、Ding、He、Lai 和 Song。

Introduction: Sepsis is a clinical syndrome characterized by dysregulation of the host immune response due to infection, resulting in life-threatening organ damage. Despite active promotion and implementation of early preventative measures and bundle treatments, sepsis continues to exhibit high morbidity and mortality rates with no optimal pharmacological intervention available. Lobetyolin (LBT), the crucial component of polyacetylenes found in Codonopsis pilosula, has been scientifically proven to possess potent antioxidant and antitumor properties. However, its therapeutic potential for sepsis remains unknown. Methods: The mice received pretreatment with intraperitoneal injections of LBT, followed by injection with lipopolysaccharide (LPS) to induce sepsis. Peripheral blood samples were collected to detect TNF-α, IL-1β, and IL-6 levels. The survival status of different groups was recorded at various time intervals. RNA-Seq was utilized for the analysis of gene expression in peritoneal macrophages treated with LBT or LPS. Results: In this study, we observed a significant increase in the survival rate of mice pretreated with LBT in LPS induced sepsis mouse model. LBT demonstrated a remarkable reduction in the production of IL-6, TNF-α, and IL-1β in the serum, along with mitigated lung and liver tissue damage characterized by reduced inflammatory cell infiltration. Additionally, through RNA-seq analysis coupled with GO and KEGG analysis, it was revealed that LBT effectively suppressed genes associated with bacterium presence, cellular response to lipopolysaccharide stimulation, as well as cytokine-cytokine receptor interaction involving Cxcl10, Tgtp1, Gbp5, Tnf, Il1b and IRF7 specifically within macrophages. We also confirmed that LBT significantly downregulates the expression of IL-6, TNF-α, and IL-1β in macrophage activation induced by LPS. Discussion: Therefore, our findings demonstrated that LBT effectively inhibits the production of inflammatory cytokines (IL-6, TNF-α, and IL-1β) and mitigates sepsis induced by LPS through modulating macrophages' ability to generate these cytokines. These results suggest that LBT holds promise as a potential therapeutic agent for sepsis treatment.Copyright © 2024 Chen, Su, Ding, He, Lai and Song.