Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Immunol. 2021 Jan 28;12:626894. doi: 10.3389/fimmu.2021.626894. eCollection 2021.
Short chain fatty acids (SCFAs) are known to be actively involved in multiple brain disorders, but their roles in sepsis-associated encephalopathy (SAE) remain unclear. Here, we investigated the neuroprotective effects of SCFAs on SAE in mice. Male C57BL/6 mice were intragastrically pretreated with SCFAs for seven successive days, and then subjected to SAE induced by cecal ligation and puncture. The behavioral impairment, neuronal degeneration, and levels of inflammatory cytokines were assessed. The expressions of tight junction (TJ) proteins, including occludin and zoula occludens-1 (ZO-1), cyclooxygenase-2 (COX-2), cluster of differentiation 11b (CD11b), and phosphorylation of JNK and NF-κB p65 in the brain, were measured by western blot and Immunofluorescence analysis. Our results showed that SCFAs significantly attenuated behavioral impairment and neuronal degeneration, and decreased the levels of IL-1β and IL-6 in the brain of SAE mice. Additionally, SCFAs upregulated the expressions of occludin and ZO-1 and downregulated the expressions of COX-2, CD11b, and phosphorylation of JNK and NF-κB p65 in the brain of SAE mice. These findings suggested that SCFAs could exert neuroprotective effects against SAE in mice.
短链脂肪酸（SCFAs）被认为积极参与多种脑部疾病，但它们在脓毒症相关性脑病（SAE）中的作用尚不清楚。在这里，我们研究了 SCFAs 对小鼠 SAE 的神经保护作用。雄性 C57BL/6 小鼠连续 7 天经胃内预处理 SCFAs，然后用盲肠结扎和穿刺法诱导 SAE。评估行为障碍、神经元变性和炎症细胞因子水平。通过 Western blot 和免疫荧光分析测量脑内紧密连接（TJ）蛋白，包括闭合蛋白和 zorla 闭合蛋白-1（ZO-1）、环氧化酶-2（COX-2）、分化群 11b（CD11b）和 JNK 和 NF-κB p65 的磷酸化。结果表明，SCFAs 显著减轻了 SAE 小鼠的行为障碍和神经元变性，降低了脑内 IL-1β和 IL-6 的水平。此外，SCFAs 上调了脑内闭合蛋白和 ZO-1 的表达，下调了 COX-2、CD11b、JNK 和 NF-κB p65 的磷酸化。这些发现表明，SCFAs 可以对小鼠 SAE 发挥神经保护作用。
