简介:脓毒症是一种临床综合征,其特征是由于感染引起的宿主免疫反应失调,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化治疗,脓毒症的发病率和死亡率仍然很高,没有最佳的药物干预.叶花素(LBT),在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,其对脓毒症的治疗潜力尚不清楚.方法:小鼠接受腹膜内注射LBT预处理,然后注射脂多糖(LPS)诱导脓毒症。收集外周血标本检测TNF-α,IL-1β,和IL-6水平。在不同的时间间隔记录不同组的生存状态。RNA-Seq用于分析用LBT或LPS处理的腹膜巨噬细胞中的基因表达。结果:在这项研究中,在LPS诱导的脓毒症小鼠模型中,我们观察到LBT预处理小鼠的存活率显着提高。LBT显示IL-6,TNF-α的产生显着减少,血清中的IL-1β,随着减轻肺和肝组织损伤的特点是减少的炎症细胞浸润。此外,通过RNA-seq分析以及GO和KEGG分析,研究表明,LBT有效抑制了与细菌存在相关的基因,细胞对脂多糖刺激的反应,以及涉及Cxcl10,Tgtp1,Gbp5,Tnf,Il1b和IRF7特异性地在巨噬细胞内。我们还证实,LBT显著下调IL-6、TNF-α的表达,和IL-1β在LPS诱导的巨噬细胞活化中的作用。讨论:因此,我们的发现表明,LBT有效抑制炎症细胞因子的产生(IL-6,TNF-α,和IL-1β),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有望成为脓毒症治疗的潜在治疗剂。
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.