Abstract：
Aged adults are prone to both short- and long-term complications following sepsis due to ineffective therapy. Phosphatidylserine (PS) is a membrane nutrient supplement known to enhance cognition and brain function, but its potential effects in treating sepsis are not well-documented. Our study aimed to explore the potential of PS in improving outcomes in sepsis and sepsis-associated encephalopathy (SAE). Middle-aged mice were administered PS for two months following induction of sepsis by lipopolysaccharides. The results indicated a significant increase in the survival rate of mice treated with PS after sepsis. Surviving mice underwent open field and shuttle box tests 45 days post-sepsis, revealing potential alleviation of neurobehavioral impairments due to PS pretreatment. Analysis at 60 days post-sepsis euthanasia showed reduced cleaved-caspase 3 in neurons and glial cell markers in the PS-treated group compared to the untreated sepsis group. Furthermore, PS administration effectively reduced proinflammatory cytokine gene expression in the hippocampus of mice with SAE, potentially inhibiting the TBK1/NLRP3/ASC signaling pathway. In the gut, PS pretreatment modulated β-diversity while maintaining jejunal morphology and colon ZO-1 expression, without significantly affecting α-diversity indices. Our findings suggest that PS administration improves survival rates, modulates the gut microbiome, preserves gut integrity, and ameliorates brain pathology in survived mice after sepsis. Importantly, these findings have significant implications for sepsis treatment and cognitive function preservation in aging individuals, providing new insights and sparking further interest and investigation into the potential of PS in sepsis treatment.
摘要：
由于无效的治疗，老年人在败血症后容易出现短期和长期并发症。磷脂酰丝氨酸（PS）是一种膜营养补充剂，可增强认知和大脑功能，但其在治疗脓毒症方面的潜在作用尚不清楚.我们的研究旨在探讨PS在改善脓毒症和脓毒症相关性脑病（SAE）预后方面的潜力。在脂多糖诱导脓毒症后，向中年小鼠施用PS两个月。结果表明,在脓毒症后用PS处理的小鼠的存活率显著增加。存活的小鼠在败血症后45天进行了野外和穿梭箱测试，揭示由于PS预处理导致的神经行为障碍的潜在缓解。在败血症安乐死后60天的分析显示,与未处理的败血症组相比,PS处理组的神经元和神经胶质细胞标志物中切割的半胱天冬酶3减少。此外，PS给药有效降低SAE小鼠海马促炎细胞因子基因表达,可能抑制TBK1/NLRP3/ASC信号通路。在肠子里，PS预处理调节β-多样性，同时维持空肠形态和结肠ZO-1表达，而不会显著影响α-多样性指数。我们的研究结果表明，PS管理提高生存率，调节肠道微生物组，保持肠道完整性，并改善败血症后存活小鼠的脑病理学。重要的是,这些发现对衰老个体的败血症治疗和认知功能保护具有重要意义，提供新的见解，并激发进一步的兴趣和研究PS在脓毒症治疗中的潜力。
