PDF(Pubmed)
Abstract：
Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.
摘要：
脓毒症相关脑病（SAE）是脓毒症患者死亡的重要原因。尽管进行了广泛的研究,其确切原因尚不清楚。我们先前的研究表明非肝性高氨血症（NHH）与SAE之间存在关系。本研究旨在探讨NHH与SAE之间的关系以及引起认知障碍的潜在机制。在体内实验结果中，中度盲肠结扎穿孔(CLP)小鼠肝脏无明显异常;海马组织和血清中的氨水平升高。ELISA研究表明，CLP小鼠的粪便微生物群移植可以降低氨水平。氨水平的降低通过行为改善CLP小鼠的认知功能障碍和神经功能缺损，神经影像学,和分子生物学研究。进一步的研究表明，氨进入大脑调节星形胶质细胞水通道蛋白4（AQP4）的表达，这可能是CLP小鼠脑功能障碍的潜在机制。体外实验结果表明,氨水上调星形胶质细胞AQP4的表达,导致星形胶质细胞损伤。这项研究的结果表明，氨通过肠脑轴上调星形胶质细胞AQP4的表达，这可能是SAE发生的潜在机制。
