PDF(Pubmed)
Abstract：
The study investigated the protective effects and mechanisms of probiotics in conjunction with an anti-PD-L1 antibody on the immune functions of septic mice. Sixty-four mice were assigned to sepsis groups receiving vehicle, probiotics, and anti-PD-L1 antibody individually or in combination, with healthy mice as controls. Sepsis was induced by cecal ligation and puncture (CLP), followed by intraperitoneal Lipopolysaccharide (LPS) injection. Blood and tissues were collected one day post-injection for detecting inflammation-related cytokines, Treg, PI3K/Akt pathway-related protein expression, and lung tissue pathology. The survival time of the remaining ten mice was recorded over seven days. Compared to healthy mice, septic mice given PBS exhibited significantly different serum levels of IL-6, IL-8, IL-17, IL-10, and IFN-γ (all p < 0.001). Treatment with anti-PD-L1 antibody combined with probiotics significantly increased the 7-day survival rate in septic mice, accompanied by decreased pro-inflammatory cytokines, increased anti-inflammatory cytokines, improved oxidative stress, reduced lung injury, and enhanced Th17/Treg balance. This combined therapy demonstrated superior efficacy compared to antibodies or probiotics alone. Additionally, it facilitated peripheral blood polymorphonuclear neutrophil apoptosis, enhancing protection by blocking PD-L1 function and inhibiting PI3K-dependent AKT phosphorylation. In conclusion, combining probiotics with an anti-PD-L1 antibody enhances protective effects in septic mice by reducing serum inflammatory factors, promoting neutrophil apoptosis, regulating Th17/Treg balance, and inhibiting the PI3K/Akt pathway.
摘要：
该研究调查了益生菌与抗PD-L1抗体联合对脓毒症小鼠免疫功能的保护作用和机制。64只小鼠被分配到接受媒介物的脓毒症组，益生菌，和抗PD-L1抗体单独或组合，以健康小鼠为对照。盲肠结扎穿孔术（CLP）诱发脓毒症，然后腹膜内注射脂多糖(LPS)。注射后一天收集血液和组织用于检测炎症相关细胞因子，Treg,PI3K/Akt通路相关蛋白表达,和肺组织病理学。记录剩余10只小鼠7天的存活时间。与健康小鼠相比，给予PBS的脓毒症小鼠表现出显著不同的血清IL-6，IL-8，IL-17，IL-10和IFN-γ水平（所有p<0.001）。抗PD-L1抗体联合益生菌治疗可显着提高脓毒症小鼠的7天生存率，伴随着促炎细胞因子的减少，增加抗炎细胞因子，改善氧化应激，减少肺损伤，增强Th17/Treg平衡。与单独的抗体或益生菌相比,该组合疗法显示出优异的功效。此外,它促进外周血中性粒细胞凋亡，通过阻断PD-L1功能和抑制PI3K依赖性AKT磷酸化来增强保护作用。总之,益生菌与抗PD-L1抗体结合通过降低血清炎症因子增强脓毒症小鼠的保护作用，促进中性粒细胞凋亡，调节Th17/Treg平衡，并抑制PI3K/Akt途径。
