Abstract：
BACKGROUND: Sepsis is a syndrome that occurs following an infection and marked by severe inflammatory responses, and if not treated in time, it can lead to multi-organ failure syndrome and death. This study examines the effects of a novel combination therapy using azithromycin and mesenchymal stem cell-derived extracellular vesicles (EVs) on a cecal ligation and puncture (CLP) model of sepsis.
METHODS: Human Wharton\'s jelly-mesenchymal stem cells were cultured, characterized, and used to extract EVs. The CLP sepsis model was induced in mice, followed by treatments: saline, AZM, EVs, and combination therapy (A+E). Clinical sepsis scores were recorded 24 h post-treatment. Serum, peritoneal fluid, and organ tissues (kidney, liver, lung) were collected and analyzed for biochemical parameters (AST ALT, and creatinine), inflammatory markers, bacterial load, and histopathological changes.
RESULTS: The A+E combined treatment improved the clinical scores of septic mice. The administration of A+E reduced bacterial loads in the peritoneum of septic mice, contributing to effective control of infection. Inflammatory markers of neutrophils-to-lymphocytes ratio (NLR) and TNF-α serum levels were significantly lower in the combinational therapy group, indicating significant anti-inflammatory effect of this combination. Additionally, combination of AZM and EVs alleviated organ damage mainly within liver, kidneys and lungs. Based on histopathological assessments and biochemical parameters, there was diminished tissue damage as well as reduced inflammation, which is correlated with improved functions of these vital organs.
CONCLUSIONS: The combined use of azithromycin and EVs offers a promising therapeutic approach for sepsis by effectively controlling infection and modulating the inflammatory response.
METHODS: Human Wharton\'s jelly-mesenchymal stem cells were cultured, characterized, and used to extract EVs. The CLP sepsis model was induced in mice, followed by treatments: saline, AZM, EVs, and combination therapy (A+E). Clinical sepsis scores were recorded 24 h post-treatment. Serum, peritoneal fluid, and organ tissues (kidney, liver, lung) were collected and analyzed for biochemical parameters (AST ALT, and creatinine), inflammatory markers, bacterial load, and histopathological changes.
RESULTS: The A+E combined treatment improved the clinical scores of septic mice. The administration of A+E reduced bacterial loads in the peritoneum of septic mice, contributing to effective control of infection. Inflammatory markers of neutrophils-to-lymphocytes ratio (NLR) and TNF-α serum levels were significantly lower in the combinational therapy group, indicating significant anti-inflammatory effect of this combination. Additionally, combination of AZM and EVs alleviated organ damage mainly within liver, kidneys and lungs. Based on histopathological assessments and biochemical parameters, there was diminished tissue damage as well as reduced inflammation, which is correlated with improved functions of these vital organs.
CONCLUSIONS: The combined use of azithromycin and EVs offers a promising therapeutic approach for sepsis by effectively controlling infection and modulating the inflammatory response.
摘要：
背景：脓毒症是一种感染后发生的综合征，以严重的炎症反应为特征，如果不及时治疗，它可以导致多器官衰竭综合征和死亡。这项研究检查了使用阿奇霉素和间充质干细胞衍生的细胞外囊泡（EV）的新型联合疗法对盲肠结扎和穿孔（CLP）脓毒症模型的影响。
方法：培养人沃顿胶质间充质干细胞，characterized,用于提取电动汽车。建立小鼠CLP脓毒症模型,其次是治疗：盐水，AZM,电动汽车,和联合治疗（A+E）。治疗后24小时记录临床脓毒症评分。血清,腹膜液,和器官组织(肾脏，肝脏,肺）收集并分析生化参数（ASTALT，和肌酐），炎症标志物，细菌负荷，和组织病理学变化。
结果：A+E联合治疗改善了脓毒症小鼠的临床评分。A+E的给药减少了脓毒症小鼠腹膜中的细菌负荷，有助于有效控制感染。联合治疗组的炎性标志物中性粒细胞与淋巴细胞比值(NLR)和TNF-α血清水平显著降低,表明该组合的显着抗炎作用。此外,AZM和EV的组合减轻了主要在肝脏内的器官损伤，肾脏和肺。根据组织病理学评估和生化参数，组织损伤减少，炎症减少，这与这些重要器官的功能改善有关。
结论：阿奇霉素和EV的联合使用通过有效控制感染和调节炎症反应为脓毒症提供了一种有希望的治疗方法。
方法：培养人沃顿胶质间充质干细胞，characterized,用于提取电动汽车。建立小鼠CLP脓毒症模型,其次是治疗：盐水，AZM,电动汽车,和联合治疗（A+E）。治疗后24小时记录临床脓毒症评分。血清,腹膜液,和器官组织(肾脏，肝脏,肺）收集并分析生化参数（ASTALT，和肌酐），炎症标志物，细菌负荷，和组织病理学变化。
结果：A+E联合治疗改善了脓毒症小鼠的临床评分。A+E的给药减少了脓毒症小鼠腹膜中的细菌负荷，有助于有效控制感染。联合治疗组的炎性标志物中性粒细胞与淋巴细胞比值(NLR)和TNF-α血清水平显著降低,表明该组合的显着抗炎作用。此外,AZM和EV的组合减轻了主要在肝脏内的器官损伤，肾脏和肺。根据组织病理学评估和生化参数，组织损伤减少，炎症减少，这与这些重要器官的功能改善有关。
结论：阿奇霉素和EV的联合使用通过有效控制感染和调节炎症反应为脓毒症提供了一种有希望的治疗方法。
