基于脑–肠轴理论探析阿尔茨海默病作用机制

To Explore the Mechanism of Alzheimer’s Disease Based on Brain-Gut Axis Theory

摘要: 阿尔茨海默病(Alzheimer’s disease, AD)是一种神经退行性疾病，主要表现为认知障碍。近年来出现的脑–肠轴学说提供了AD新的研究方向。老年时期微生物群组成的显着变化可能在神经退行性疾病的发展中发挥重要作用，AD与衰老密切相关。本文通过微生物作用探讨脑肠轴与AD之间的联系，结合AD的发病机制与脑–肠轴学说的基本原理，对微生物的作用机制论述脑–肠轴学说的出现对AD的影响。AD病理包括淀粉样蛋白假说、tau蛋白过度磷酸化以及神经炎症等。微生物异常可介导神经炎症，进而影响AD病理进程。肠道微生物及其代谢产物影响血脑屏障(blood brain barrier, BBB)通透性，BBB调节功能受损，微生物及其有害代谢产物进入并影响大脑活动。因此，肠道微生物群的恶化可能导致脑功能障碍。而甘露特钠作为国际首个靶向脑肠轴的AD治疗新药，可预见的未来靶向肠道菌群治疗AD可能成重要的研究方向，为药物研发提供了全新的干预方法。

Abstract: Alzheimer’s disease (AD) is a kind of neurodegenerative disease, mainly manifested by cognitive impairment. In recent years, the brain-gut axis theory has provided a new research direction for AD. Significant changes in the composition of the microbiome in old age may play an important role in the development of neurodegenerative diseases, and AD is closely associated with aging. In this paper, the relationship between brain-gut axis and AD was investigated through microbial action. This paper combined the pathogenesis of AD with the basic principle of brain-gut axis theory, and discussed the effect of brain-gut axis theory on AD by the mechanism of microbial action. The pathology of AD includes amyloid hypothesis, tau hyperphosphorylation and neuroinflammation. Microbial abnormalities can mediate neuroinflammation, and then affect the pathological process of AD. Intestinal microorganisms and their metabolites affect the permeability of blood brain barrier (BBB), and the regulatory function of BBB is impaired. Microorganisms and their harmful metabolites enter and affect brain activities. Thus, deterioration of the gut microbiome may lead to brain dysfunction. As the first AD treatment drug targeting brain-gut axis in the world, Sodium Oligomannate become an important research direction for the treatment of AD targeting intestinal flora in the foreseeable future, providing a new intervention method for drug development.