二氯乙酸（DCA）是一种丙酮酸脱氢酶激酶抑制剂，常用于治疗乳酸性酸中毒和恶性肿瘤。越来越多的研究表明 DCA 具有神经保护作用。在这里，我们探讨了 DCA 在脓毒症相关脑病 (SAE) 中的作用和机制。单细胞分析用于确定 PDK4 在 SAE 中的重要作用并鉴定细胞类型。 GO 和 GSEA 分析用于确定 DCA 与细胞焦亡之间的相关性。通过LPS  ATP刺激，建立小胶质细胞焦亡模型，观察DCA干预下细胞内焦亡相关蛋白的表达水平，并进一步检测细胞内ROS和JC-1的变化。此外，简单构建了小胶质细胞和神经元的共培养环境，以评估DCA对激活的小胶质细胞介导的神经元凋亡的影响。最后采用新物体识别测试和Morris水迷宫探讨DCA干预后对不同组小鼠认知功能的影响。基于上述实验，本研究得出结论，DCA可以提高外周和中枢M1巨噬细胞的比例，通过ROS和线粒体膜电位（MMP）抑制NLRP3介导的细胞焦亡。 DCA可以减少SAE引起的神经元死亡并改善LPS小鼠的认知功能。在 SAE 中，DCA 可能是治疗小胶质细胞介导的神经炎症的潜在候选药物。© 2024。作者。

Dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, is often used to treat lactic acidosis and malignant tumors. Increasing studies have shown that DCA has neuroprotective effects. Here, we explored the role and mechanism of DCA in Sepsis associated encephalopathy (SAE). Single-cell analysis was used to determine the important role of PDK4 in SAE and identify the cell type. GO and GSEA analysis were used to determine the correlation between DCA and pyroptosis. Through LPS + ATP stimulation, a microglia pyroptosis model was established to observe the expression level of intracellular pyroptosis-related proteins under DCA intervention, and further detect the changes in intracellular ROS and JC-1. Additionally, a co-culture environment of microglia and neuron was simply constructed to evaluate the effect of DCA on activated microglia-mediated neuronal apoptosis. Finally, Novel object recognition test and the Morris water maze were used to explore the effect of DCA on cognitive function in mice from different groups after intervention. Based on the above experiments, this study concludes that DCA can improve the ratio of peripheral and central M1 macrophages, inhibit NLRP3-mediated pyroptosis through ROS and mitochondrial membrane potential (MMP). DCA can reduce neuron death caused by SAE and improve cognitive function in LPS mice. In SAE, DCA may be a potential candidate drug for the treatment of microglia-mediated neuroinflammation.© 2024. The Author(s).