基于脑肠轴探讨中药治疗卒中后抑郁的作用机制

Action Mechanism of Chinese Medicinal in Treating Post-Stroke Depression Based on Brain-Gut Axis

脑肠轴学说认为,大脑与肠道之间存在一种双向调节通道,病理状态下二者亦相互影响,基于脑肠轴治疗神经、精神和消化系统疾病仍然是目前临床研究的热点。卒中后抑郁(PSD)是脑卒中最常见的并发症之一,大量研究发现其与脑肠轴功能失调密切相关,生理状态下肠道微生物在调节脑肠轴的平衡中发挥着重要的作用,具有合成或调节神经递质分泌、降低炎症因子、调节HPA轴等作用,从而影响大脑的认知、情感及学习功能。脑卒中后机体发生一系列的反应,导致肠道菌群的数量、构成及代谢发生变化,该变化又通过肠神经系统、自主神经系统、内分泌系统、免疫系统等通路对大脑的情感调节产生不利影响,进一步促进了PSD的发生,即脑病及肠,肠病及脑,二者互相影响。脑肠轴亦与中医理论相符,临床多以疏肝、健脾、养心,兼以祛瘀化痰为大法治疗PSD,临床疗效显著,但其作用机制尚未完全明确。本文通过梳理PSD发病的危险因素、发病机制、中医对脑肠轴的认识,基于脑肠轴探讨和总结中药复方在治疗PSD中的作用机制,发现大量临床及动物试验均证实了中药复方能通过调节肠道菌群发挥抑制炎症反应、调节HPA轴、增加脑内5-羟色胺等神经递质的分泌,多靶点地参与PSD的治疗。

The theory of brain-gut axis regards that there is a two-way adjustment channel between brain and intestines and they also influence each other in pathological condition.The treatment for neuropathy diseases,mental diseases and digestive system disease based on brain-gut axis is still the clinical research hot topic at present.Post-stroke depression(PSD)is one of the most common complications of stroke,and a large number of studies have found that it is closely related to the dysfunction of brain-gut axis.Under physiological conditions,gut microbes play an important role in regulating the balance of brain-gut axis,which can synthesize or regulate the secretion of neurotransmitters,reduce the inflammatory factors,and regulate the HPA axis to affect cognitive,emotional and learning functions of brain.After stroke,a series of reactions take place within body,which lead to some changes in quantity,composition and metabolism of intestinal flora and these changes have negative effects on emotional regulation through enteric nervous system,autonomic nervous system,endocrine system and other pathways,which further promotes the occurrence of PSD.It is called that diseases of brain can result in diseases of intestines,diseases of intestines also can result in diseases of brain,and they influence each other.At the same time,brain-gut axis was also consistent with the theory in TCM,TCM treats PSD in terms of soothing Liver,strengthening Spleen,nourishing Heart accompanied by removing blood stasis and resolving phlegm.The clinical effect of TCM treatment for PSD is remarkable,but the mechanism is not fully clear.This article combed the risk factors and pathogenesis of PSD,TCM understanding in brain-gut axis,it was found that TCM compound could inhibit inflammatory response,regulate HPA axis and increase secretion of neurotransmitters,such as 5-HT,in brain by regulating intestinal microbiota,and multiple targets were involved in treatment of PSD,based on brain-gut axis in clinical practice and animal experiment.