Chen Zhonghua, Su Yixin, Ding Jingtong, He Jia, Lai Lihua, Song Yinjing
Department of Emergency, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China.
Front Pharmacol. 2024 May 10;15:1405163. doi: 10.3389/fphar.2024.1405163. eCollection 2024.
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 , has been scientifically proven to possess potent antioxidant and antitumor properties. However, its therapeutic potential for sepsis remains unknown. 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. 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 and 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. 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.
脓毒症是一种临床综合征，其特征是由于感染导致宿主免疫反应失调，进而造成危及生命的器官损伤。尽管积极推广和实施了早期预防措施和集束治疗，但脓毒症的发病率和死亡率仍然很高，且尚无最佳的药物干预措施。洛贝蒂olin（LBT）是中发现的聚乙炔的关键成分，已被科学证明具有强大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。小鼠接受腹腔注射LBT预处理，然后注射脂多糖（LPS）以诱导脓毒症。采集外周血样本检测TNF-α、IL-1β和IL-6水平。记录不同组在不同时间间隔的存活状态。利用RNA测序分析用LBT或LPS处理的腹腔巨噬细胞中的基因表达。在本研究中，我们观察到在LPS诱导的脓毒症小鼠模型中，用LBT预处理的小鼠存活率显著提高。LBT使血清中IL-6、TNF-α和IL-1β的产生显著减少，同时减轻了以炎症细胞浸润减少为特征的肺和肝组织损伤。此外，通过RNA测序分析以及GO和KEGG分析发现，LBT有效地抑制了与细菌存在、细胞对脂多糖刺激的反应以及巨噬细胞内特别是涉及和的细胞因子-细胞因子受体相互作用相关的基因。我们还证实，LBT显著下调LPS诱导的巨噬细胞活化中IL-6、TNF-α和IL-1β的表达。因此，我们的研究结果表明，LBT通过调节巨噬细胞产生这些细胞因子的能力，有效抑制炎症细胞因子（IL-6、TNF-α和IL-1β）的产生，并减轻LPS诱导的脓毒症。这些结果表明，LBT有望成为治疗脓毒症的潜在治疗药物。
