从肠道微生态研究朝医“药乃局限于人”四象药性观的作用机制

That “medicine is limited to human” is unique to the SaSang Medicine perspective of the Korean Medicine. It is featured as the medication view that some traditional Chinese medicine can work as prevention and treatment to one of the four constitutions SaSang Human (Taeeumin, Soeumin, Taeyang, and Shaoyang, which is classified by the Korean Medicine), while they can not cure or, instead, results in severe side effect on some others. This medication view can effectively guide clinical medications, however currently, the concrete mechanism remains unknown yet and affacts its academic development. Traditional Chinese medicine is primarily metabolized through the intestinal metabolism, and intestinal flora play an important role in the metabolism of traditional Chinese medicine. New research is showing that closely associated with ntestinal flora constitution .Based on this fact, it is proposed the hypothesis that “there exists some certain correlation between the SaSang Constitutions of the Korean Medicine and intestinal flora”. With the employment of bioinformatics analyzing technique, such as PCR-DGGE molecular ecology, 454 pyrosequencing method and so on, the DNA sequence of intestinal flora of SaSang Constitutions in Korean Medicine can be determined, and the fingerprint and phylogenetic tree of the Korean intestinal flora will be constructed. Furthermore, it applies the multivariate statistical method, such as Unifrac, PCA and OPLS-DA, to explore and analyze the diversity and difference of the intestinal flora in the SaSang Constitutions of the Korean Medicine and the distribution regularities of the flora among these four constitutions, reveals the mechanism of action of the view that “medicine is limited to human” of the Korean Medicine, expounds the scientific connotation of the SaSang Constitutions theory of the Korean Medicine, and provides new ideas for the distinguishing research of the four constitutions of the Korean Medicine.

“药乃局限于人”是朝医学独有的四象药性观，是指一些中药对朝医四象人（把人分为太阴人、少阴人、太阳人和少阳人四种）中的一种人群有治疗和预防作用，而对其他人群无治疗作用或反而出现严重副作用的用药观点，可有效指导临床用药，但因生物学机制不清，影响了朝医学发展。肠道代谢是中药代谢的主要途径，而肠道菌群对中药的代谢起至关重要作用。最新研究表明，体质与肠道菌群关系密切。鉴此，提出“朝医四象人体质与肠道菌群具有一定相关性”的假说，拟通过采用PCR-DGGE分子生态学、454焦磷酸测序法等生物信息学分析技术，测定朝医四象人的肠道菌群DNA序列、构建肠道菌群指纹图谱及生物进化树，并运用Unifrac、PCA和OPLS-DA等多元统计法探索朝医四象人肠道菌群的多样性及差异性，以及四种人之间菌群的分布规律，揭示朝医学“药乃局限于人”的作用机制，阐释朝医四象人体质理论的科学内涵，为今后朝医学辨象研究提供新的思路。

“药乃局限于人”是朝医学独有的四象药性观，是指一些中药对朝医四象人中的一种人群有治疗和预防作用，而对其他人群无治疗作用或反而出现严重副作用的用药观点，可有效指导临床用药，但因生物学机制不清，影响了朝医学发展。本研究通过收集朝医四象人(太阴人、少阴人、少阳人、太阳人)四种不同体质的粪便样本，基于16S扩增高通量测序技术、SPSS18.0统计软件及GraphPad Prism作图软件等，对四种体质人群的性别、身高、年龄、体重、体质指数、血糖、血脂及肠道微生群落组成结构、丰度等进行对比分析，发现朝医四象人四种体质的体重、BMI及甘油三酯存在显著差异（P<0.05），四种体质人群的肠道微生物的丰富度、多样性以及后壁菌门和拟杆菌门丰度比值均有所不同，且存在24种显著差异的肠道微生物（p<0.05），而产粪甾醇真细菌菌群是朝医四象人体质的显著差异菌群。研究结果表明，朝医四象人体质与肠道菌群存在密切关系，不同体质间肠道微生物存在显著差异，厚壁菌门和拟杆菌门丰度比值可能与四种人群体重、BMI及血脂存在差异有关，而产粪甾醇真细菌菌群可能是四种人群区别的主要靶点，提示朝医学中“药乃局限于人”即不同药物在不同体质中发挥作用不一，可能与后壁菌门、拟杆菌门及产粪甾醇真细菌菌群有关。本项目研究对揭示朝医学“药乃局限于人”四象药性观的生物学作用机制，对阐明朝医四象人体质理论的科学内涵具有重要意义，并为朝医学辨象研究提供了新的思路。