尽管死亡率很高，脓毒症缺乏具体有效的治疗方案。传统抗生素，如TIENAM（TIE；注射用亚胺培南西司他丁钠），由于细菌耐药性的出现而面临挑战，这降低了其有效性并产生不良反应。解决耐药性和明智地使用药物至关重要。我们的研究表明，芦荟素 (Alo) 可以显着提高脓毒症小鼠的存活率并减少炎症和细菌负荷，表现出强大的抗菌活性。在盲肠结扎穿刺 (CLP) 诱导的脓毒症模型中使用协同 Alo TIE 方案，与单独使用 CLP 组相比，我们观察到 72 小时内存活率从 10% 显着提高到 75%。这种联合疗法还调节炎症标志物白细胞介素 (IL)-6、IL-1β 和肿瘤坏死因子 (TNF)-α，减轻组织损伤，通过降低 NK 调节免疫细胞，激活 CD8 和 CD4 T 细胞，同时增加腹膜巨噬细胞，并减少腹膜腔内的细菌负荷。我们注意到治疗后腹腔微生物群组成发生显着变化，有害细菌（例如 Lachnospiraceae_NK4A136_group、克雷伯氏菌、芽孢杆菌和大肠杆菌）减少，而有益细菌（例如乳杆菌和粘螺菌）增加。我们的研究强调了 Alo 与 TIE 联合治疗败血症的功效，并为进一步研究和潜在的临床应用铺平了道路，旨在克服 TIE 的局限性并增强 Alo 的治疗前景。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.Copyright © 2024 Elsevier B.V. All rights reserved.