【摘要】 目的 研究注射用益气复脉(冻干)(YQFM)对脓毒症免疫功能障碍和心功能障碍疗效机制。方法 使用网络药理学筛选YQFM主要成分红参(Radix Et Rhizoma Ginsen Rubra)、麦冬(Radix Ophiopogonis)和北五味子(Fructus Schisandrae Chinensis)的成分和靶点基因并与脓毒症靶点网络取交集获得YQFM治疗脓毒症核心靶点并进行机制功能分析。并采用LPS腹腔注射构建小鼠脓毒症模型验证YQFM对脓毒症的治疗机制。结果 网络药理学的结果表明,YQFM与脓毒症炎症相关靶点交集后,筛选出7个核心作用靶点(NFE2L2、TNF、IL1B、IL4、IFNG、NOS2、PTGS2)。这些基因与淋巴细胞的发育、凋亡以及炎症和氧化应激密切相关。动物实验证实,YQFM高剂量组显著提升心功能(P<0.001)。同时降低淋巴细胞ROS水平及凋亡率,逆转CD4~+/CD44~+与CD8~+/CD44~+T细胞耗竭。心肌病理证实YQFM减少单核细胞浸润,改善组织结构,协同缓解免疫障碍与心功能损伤。结论 YQFM在治疗脓毒症方面展现出显著的临床潜力,尤其在改善患者的免疫功能和心功能障碍方面。该研究为应用YQFM治疗脓毒症提供了全新的视角和研究方向,具有重要的临床意义。更多还原

【Abstract】 Objective To investigate the therapeutic mechanisms of Yiqi Fumai Lyophilized Injection (益气复脉, YQFM) in sepsisinduced immune dysfunction and cardiac dysfunction.Methods Network pharmacology was used to screen the active components and target genes of the primary medicinal materials of YQFM: Radix et Rhizoma Ginseng Rubra, Radix Ophiopogonis, and Fructus Schisandrae Chinensis. The intersection with sepsis-related targets identified core therapeutic targets for YQFM in sepsis. Functional and mechanistic analyses were performed. Subsequently, a murine sepsis model was established by intraperitoneal lipopolysaccharide(LPS) injection to validate the therapeutic effects and underlying mechanisms of YQFM. Results Network pharmacology analysis revealed that intersection of YQFM targets with sepsis-related inflammatory targets identified seven core therapeutic targets(NFE2L2, TNF, IL1B, IL4, IFNG, NOS2, and PTGS2). These genes are closely associated with lymphocyte development, apoptosis, as well as inflammation and oxidative stress. Animal experiments demonstrated that the high-dose YQFM group showed significantly enhanced cardiac function(P < 0. 001). Concurrently, YQFM reduced ROS levels and apoptosis rates in lymphocytes and alleviated the exhaustion of CD4~+CD44~+ and CD8~+CD44~+ T cells. Myocardial pathology further confirmed that YQFM attenuated monocyte infiltration, ameliorated tissue structure, and mitigated both immune dysfunction and cardiac injury.Conclusion YQFM demonstrates considerable therapeutic potential for sepsis, particularly in alleviating immune dysfunction and cardiac dysfunction. This study provides novel insights and research directions for the application of YQFM in sepsis management, holding significant clinical implications.更多还原