基于“三阴并调”探析黑逍遥散调控肠道菌群TMA/FMO3/TMAO代谢通路防治AD的思路与策略

Ideas and Strategies of Hei Xiaoyaosan Regulating TMA/FMO3/TMAO Metabolic Pathway of Intestinal Flora in Prevention and Treatment of Alzheimer’s Disease(AD)Based on"Simultaneous Regulation of Three Yin"of Liver,Spleen and Kidney

阿尔兹海默病(AD)作为一种神经系统退行性疾病,随着老龄化进程的加快,罹患人数逐年增长,不仅威胁患者健康甚至生命,且给患者、家庭和社会造成沉重的经济负担和精神压力。中医学将其归属于"痴呆"等范畴,传统以补肾为其治要,而基于中医基本理论并结合AD的临床表现可见,AD与肝脾密切相关,因此,肝脾肾"三阴并调"将是防治AD的重要思路,黑逍遥散作为"三阴并调"的代表名方,具有防治AD的理论、实验及临床基础。现代研究表明,Tau蛋白过度磷酸化形成的神经原纤维缠结是其主要病理特征之一,氧化三甲胺(TMAO)与Tau蛋白过磷酸化关系密切,因此,调节TMAO代谢以抑制Tau蛋白过磷酸化是防治AD的新靶点。本文基于以上理论及研究基础,提出了"黑逍遥散通过‘三阴并调’调控肠道菌群三甲胺(TMA)/肝黄素单加氧酶3(FMO3)/TMAO代谢通路进而抑制大脑海马区Tau蛋白过磷酸化,从而达到保护神经细胞,改善学习记忆,防治AD"的研究假说,将从调控肠道菌群TMA/FMO3/TMAO代谢通路进而抑制Tau蛋白过磷酸化角度探析黑逍遥散防治AD的作用及其机制,为黑逍遥散防治AD的深入研究提出新的思路与策略。

Alzheimer’s disease(AD)is a neurodegenerative disease.With the acceleration of aging process,the number of AD patients increases year by year.This threatens the health and even life of patients,and causes heavy economic burden and mental pressure to patients,families and society.In traditional Chinese medicine(TCM),AD belongs to the category of dementia,and tonifying kidney is the main treatment.Based on the basic theory of TCM and combined with clinical manifestations of AD,AD is closely correlated with liver and spleen.Therefore,"simultaneous regulation of three Yin"of liver,spleen and kidney will be an important way for the prevention and treatment of AD.Hei Xiaoyaosan,a representative prescription of"simultaneous regulation of three Yin"of liver,spleen and kidney,has theoretical,experimental and clinical basis in preventing and treating AD.Modern studies have shown that neurofibrillary tangle formed by tau hyperphosphorylation is a main pathological feature of AD,and trimethylamine oxide(TMAO)is closely related to tau hyperphosphorylation.Therefore,regulating TMAO metabolism to inhibit tau hyperphosphorylation is a new target for the prevention and treatment of AD.On the basis of the above theory and previous studies,this paper put forward the hypothesis that Hei Xiaoyaosan regulates the trimethylamine(TMA)/heparin monooxygenase 3(FMO3)/TMAO metabolic pathway of intestinal flora through"simultaneous regulation of three Yin"of liver,spleen and kidney,and then inhibits tau hyperphosphorylation in brain hippocampus,thereby protecting nerve cells,improving learning and memory,and preventing AD.This paper explored the role and mechanism of Hei Xiaoyaosan in the prevention and treatment of AD from the perspective of inhibiting tau hyperphosphorylation by regulating the TMA/FMO3/TMAO metabolic pathway of intestinal flora,which provided new ideas and strategies for in-depth study of Hei Xiaoyaosan in the prevention and treatment of AD.