肠道微生物群通过 HDAC2-ACSS2 轴调节小鼠肝缺血再灌注损伤诱导的认知功能障碍。

Gut microbiota regulates hepatic ischemia-reperfusion injury-induced cognitive dysfunction via the HDAC2-ACSS2 axis in mice.

机构信息

Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

School of Human and Social Sciences, University of West London, London, UK.

出版信息

CNS Neurosci Ther. 2024 Feb;30(2):e14610. doi: 10.1111/cns.14610.

DOI:10.1111/cns.14610

PMID:38334013

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10853894/

Abstract

AIMS

Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication.

METHODS

C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized.

RESULTS

The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus.

CONCLUSION

These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.

摘要

目的

肝血流阻断引起的肝缺血再灌注损伤（HIRI）是肝脏手术中常见的操作，不可避免。先前的研究已经证实，HIRI 引起的认知功能障碍与肠道微生物失调密切相关。本研究旨在探讨这一并发症的发生机制。

方法

C57BL/6 小鼠通过阻断肝左动脉和门静脉进行肝缺血实验。为了评估 HDAC2-ACSS2 轴，进行了肠道微生物群移植。利用酶联免疫吸附试验和 LC/MS 短链脂肪酸检测。

结果

研究结果表明，在经历肝缺血再灌注损伤的小鼠海马体中，ACSS2 的表达明显下降，这强调了该特定区域中乙酸盐代谢的受损。此外，认知障碍表型和 HDAC2-ACSS2 轴的失调也可以通过粪便微生物移植传递给无菌小鼠。酶联免疫吸附试验显示，海马体中的乙酰辅酶 A（acetyl-CoA）和乙酰化赖氨酸水平降低。