Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fanning Xu, Hui Chen, Yubo Gao, Xiaoxia Yang, Chun Zhang, Xinli Ni
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Abstract

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing.

丁酸钠通过调节肠道微生物群失衡抑制老年小鼠的星形胶质细胞活化来改善术后谵妄
术后谵妄(POD)是老年手术患者常见的并发症,由于对其病理生理机制了解不全面,有针对性的干预措施十分有限。中枢神经系统(CNS)炎症涉及神经胶质细胞(尤其是星形胶质细胞)的激活,被认为是 POD 发生的关键因素。丁酸盐是一种四碳脂肪酸,对中枢神经系统疾病有保护作用,但其缓解 POD 的潜力仍不清楚。本研究旨在探讨丁酸钠对老年小鼠 POD 的影响。行为测试(包括开阔地、Y迷宫和食物掩埋测试)表明,丁酸钠预处理可改善老年小鼠腹腔镜手术诱发的谵妄。丁酸钠预处理抑制了海马星形胶质细胞的活化,降低了白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达水平,并保护了海马神经元。此外,该研究还揭示了肠道微生物群调节与抑制星形胶质细胞活化所介导的中枢神经保护效应之间的联系。丁酸钠通过重新平衡肠道微生物群、抑制变形杆菌和放线菌、降低嗜球菌和嗜乳球菌的丰度以及增加鞘翅菌的丰度来改善肠道形态屏障。这种调节降低了肠道的通透性,限制了有毒物质进入血液,从而减少了炎症的扩散和星形胶质细胞的过度激活,产生了中枢抗炎作用。总之,丁酸钠可通过重新平衡肠道微生物群来抑制星形胶质细胞介导的神经炎症,从而改善 POD。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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