代谢综合征痰证不同脏腑病位的遗传学基础与代谢组学特征研究

Sputum is the common TCM pathology basis of metabolic syndrome (MS). The difference of the Zangfu location of phlegm syndrome is closely related to the syndrome and the prognosis of MS. Our preliminary studies have shown that: the main Zangfu locations of MS sputum syndrome are liver, gallbladder, spleen, lung, kidney, and it has been found that he susceptibility and trends of phlegm is relacted to the congenital factors, from the genetic point of view. In order to further explore the genetic basis and its metabolomics mechanism of phlegm syndromes in different disease location. Based on the previous studies, 250 MS patients with sputum phlegm syndrome were selected as subjects and 50 healthy individuals as control. With the method of syndrome elements differentiation, the phlegm syndrome patients were divided into five groups: liver, gallbladder, spleen, lung and kidney. The following studies were carried out: 1) Using ddPCR to detect the mRNA expression of peripheral blood and to study the genetics of phlegm syndromes in different location; 2) To detect the common and individual characteristics of metabonomics of different phlegm syndromes by means of NMR; 3) To establish the association between metabolites and SNPs in different Zangfu location of MS phlegm syndrome and to study the mechanism of its complication. This project takes the genetic characteristics of different Zangfu location as a starting point, observing the metabonomics related markers in different location of MS phlegm syndromes and further enriching the etiology and pathogenesis theory of phlegm syndromes, which is not only beneficial to the screening of MS susceptible population , but also provide evidence for the TCM diagnosis and prevention and treatment for the disease.

痰是代谢综合征（MS）共同的中医病理基础，痰证的病位不同与MS的症候群及其转归密切相关。申请者前期研究表明：MS痰证患者的主要病位在肝、胆、脾、肺、肾，同时从遗传学角度发现痰证的易感性及变化趋势与先天因素有关。为进一步探讨痰证不同病位的遗传学基础及其证候形成的代谢组学机制，本项目在前期研究基础上，以250例MS痰证患者为对象，50例健康人为对照，采用证素辨证法，按照痰证患者不同病位分为肝、胆、脾、肺、肾5组，进行以下研究：1）采用ddPCR检测外周血mRNA表达，研究不同病位痰证形成的遗传学基础；2）以NMR为手段检测MS痰证不同病位的代谢组学共性与个性特点；3）建立MS痰证不同病位代谢产物与SNP的关联，研究其兼杂机制。本项目以证的不同病位的遗传学特征为起点，观察MS痰证不同病位代谢组学相关标记物，进而丰富痰证病因病机理论，不仅有利于MS易患人群的筛查，也为本病辨证和中医药防治提供依据。

痰是代谢综合征（MS）共同的中医病理基础，痰证的病位不同与MS的症候群及其转归密切相关。申请者前期研究表明：MS痰证患者的主要病位各异，同时从遗传学角度发现痰证的易感性及变化趋势与先天因素有关。为进一步探讨痰证不同病位的遗传学基础及其证候形成的代谢组学机制，本项目在前期研究基础上，以225例MS痰证患者为对象，45例健康人为对照，采用证素辨证法，按照痰证患者不同病位分为肝、脾、肾、肺、心5组，进行以下研究：（1）采用q-PCR检测外周血mRNA表达，研究不同病位痰证形成的遗传学基础；（2）以LC-MS为手段检测MS痰证不同病位的代谢组学共性与个性特点；（3）建立MS痰证不同病位代谢产物与SNP的关联，研究其兼杂机制。结果发现：（1）痰证不同病位的证候存在共性与个性的特征，阐明痰证不同病位形成的证候学基础，进一步丰富本病的病因病机理；（2）痰证不同病位的形成与IGF2BP2、FTO、CDKN2A、PPARG基因 mRNA 的表达存在一定关系，初步揭示了痰证不同病位在分子生物学上的差异。（3）1）痰证脾、肝、肾、肺、心病位的代谢组学共性特征是均以脂质、氨基酸、甘油磷脂代谢紊乱为主，不同病位间的各种代谢产物相互作用，相互影响。2）痰证脾、肝、肾、肺、心病位的个性特征是脾、肝、肾、肺、心病位分别有270、256、214、202、211种可能的特征性代谢产物，这些代谢产物可能是痰证脾、肝、肾、肺、心病位的客观物质基础。3)脾、肝、肾、肺、心病位均有其特征性代谢通路，这些代谢通路可能可以作为探索痰证脾、肝、肾、肺、心中医病位实质的切入点;（4）痰证不同病位的相关基因 SNP 位点与痰证不同病位的差异代谢产物之间的存在相关性。本项目以证的不同病位的遗传学特征为起点，观察MS痰证不同病位代谢组学相关标记物，进而丰富痰证病因病机理论，不仅有利于MS易患人群的筛查，也为本病辨证和中医药防治提供依据。