基于肠道菌群失衡探讨脾病“脉道不利”的科学内涵

Exploration of spleen diseases leading to ’unsmooth pulse’ based on unbalancing of intestinal microbiota

脾主运化水谷,布散精微,维持肠道菌群平衡。嗜食肥甘厚味,脾失健运,肠道菌群紊乱,影响脂质代谢,痰浊内生,引发动脉粥样硬化(AS)。肠道菌群失衡与高密度脂蛋白(HDL)最为密切,肠道菌群的代谢产物引发氧化炎性反应,促使HDL氧化生成变"质"的dyHDL,并影响HDL不同亚类构成及组分,抑制胆固醇逆向转运(RCT)致AS。应用健脾祛痰中药可能通过调节肠道菌群构成与丰度,减少氧化三甲胺(TMAO)生成,纠正HDL亚类构成与组分,从而起到抗AS的作用。以肠道菌群为切入点,从dyHDL生成的关键环节入手,利用宏基因组测序、LC/MS等技术,定位肠道菌群致病菌与益生菌,并提取分离HDL,探讨不同亚类dyHDL组分的变化,以及由此引发的AS改变,阐明健脾祛痰中药通过改变肠道菌群调节dyHDL抗AS的分子机制,为中医以肠道菌群为靶点"从脾论治"动脉粥样硬化性疾病提供实验依据。

Spleen accounts for digesting,absorbing,transporting,and spreading water and nutrition to maintain the balance of intestinal microbiota.Indulging in sweets and greasy foods will lead to disorder of spleen function and intestinal microbiota,as well as abnormal lipids metabolism and phlegm turbidity stagnation,finally cause atherosclerosis.Intestinal microbiota disorder is most closely related to HDL.Metabolism products of intestinal microbiota will induce inflammation,facilitate the transformation of oxidated HDL into dysfunctional HDL,influence different HDL sub-types and components,inhibit RCT from transforming into AS.Application of invigorating the spleen and expelling phlegm formula may regulate the composition and abundance of intestinal flora,reduce TMAO generation,correct the sub-type composition and components of HDL,and consequently reduce atherosclerosis.Our research took the intestinal microbiota as a focus and started with the key steps of dyHDL production.We used metagenomic sequencing,LC/MS and other technologies to locate intestinal microbiota pathogens and probiotics and to extract and separate HDL.We investigated the changes of dyHDL sub-types components and the consequent changes in AS in order to clarify the molecular mechanism and to provide experimental evidence for‘treatment from spleen perspective’regulating dyHDL through changing intestinal microflora.