基于NMR和HPLC技术的维汉民族冠心病秽浊痰阻证代谢特征与地域因素交互作用研究

Many study confirmed that there are characteristic differences among different ethnic population in disease-related predisposing genes due to genetic heterogeneity and special regional factors．Early studies show that the incidence of coronary heart disease(CHD) is higher in Xinjiang than that in other province,and the pattern of TCM syndrome of CHD present a special regional feature，which the Huizhuotanzu type is the leading TCM syndrome type(46.7%)，esult from such special regional factors as cold and arid Climate，multiethnic aggregation，various folk custom and diet Habits．.Our study aim to explore the genetic differences of TCM Syndrome (Huizhuotanzu type and Non-Huizhuotanzu type) between Uygur and Han population，assay the metabolites production in serum and urine sample using Nuclear magnetic resonance(NMR)，and High performance liquid chromatography(HPLC)，statistically analyzed the differences and relations in metabolism pathway of CHD in Uygur and Han population with a TCM syndrome type of Huizhuoitanzu，or Non-Huizhuotanzu,respectively．.Biologically offer the evidence for the TCM theory of the same disease with different syndromes，analyze the transaction and interaction amonng the regional factors．.Our study based on the special regional characteristc of TCM sydrome type of CHD in Uygur and Han population，demonstrate the contribution of special regional characteristic of patterns of TCM syndrome to the pathogenesis of CHD with Huizhuotanzu type,experimentally verify the TCM theory of “Same disease with different syndromes”，established an evidence-based strategy of prevention and treatment on coronary heart disease correspond to the special regional environment in Xinjiang region．

新疆因其特殊地域性因素（气候寒冷干燥、多民族聚集、不同民俗及饮食习惯等）及不同民族的遗传特征，冠心病发病率高于全国且中医证型具地域特点。前期研究证实，秽浊痰阻证为新疆冠心病特有证型，占冠心病患者的46.7%，说明特殊地域因素及不同种族遗传的异质性等导致不同民族对疾病存在着不同的易感基因与遗传特性。本研究以维、汉民族冠心病秽浊痰阻证与非秽浊痰阻证患者为研究对象，采用核磁共振波普技术（nuclear magnetic resonance，NMR）和高效液相色谱技术(high performance liquid chromatography，HPLC)检测血浆、尿液代谢产物，通过代谢通路分析及关联分析，了解维、汉民族冠心病秽浊痰阻证和非秽浊痰阻证患者代谢物谱的特征，并比较其差异性，揭示冠心病秽浊痰阻证代谢变化特点和机制，阐明维、汉民族冠心病秽浊痰阻证和非秽浊痰阻证“同病异证”的理论基础。

背景：新疆具有特殊地域性因素和不同民族遗传特征，冠心病（CHD）发病率高于全国且中医证型具有地域特点。研究内容：纳入CHD秽浊痰阻证、非秽浊痰阻证及健康组各228例、174例及225例，采用病例调查法分析三组人群的临床特征，应用液质联用LC-MS技术定量分析三组血、尿液样本，研究CHD秽浊痰阻证代谢相关危险因素的分布规律，探究其血、尿液代谢组学特点。结果：（1）病例调查结果：①CHD秽浊痰阻证与非秽浊痰阻证代谢水平比较：秽浊痰阻证TG、TC、LDL-C、FBG、UA及FIB水平显著高于非秽浊痰阻证；②不同年龄组CHD秽浊痰阻证与非秽浊痰阻证代谢因素比较：同年龄段（66-75岁）秽浊痰阻证GLU、TG、LDL-C、TSH高于非秽浊痰阻证组；秽浊痰阻证组TG、LDL-C、TSH指标随增龄变化呈上升趋势，HDL-C、游离T3随增龄变化呈下降趋势。（2）血清代谢组学分析：①CHD秽浊痰阻证组与健康组差异表达的代谢物主要富集在淀粉和蔗糖代谢、碳水化合物的消化和吸收、蛋白质消化吸收、脂肪酸合成等代谢通路上；②CHD非秽浊痰阻证组与健康组差异表达的代谢物主要富集在类固醇激素、味觉传导及胆汁酸合成的代谢通路上；③CHD秽浊痰阻证组与非秽浊痰阻证组血清差异表达代谢物主要富集在脂肪酸合成及不饱和脂肪酸合成等代谢通路上。（3）尿液代谢组学分析：①CHD秽浊痰阻证组与健康组尿液差异表达的代谢物主要富集在胆汁分泌、烟酸盐合成等代谢通路上；②CHD非秽浊痰阻证组与健康组尿液中差异表达的代谢物主要富集在烟酸、烟酰胺代谢和乙醛酸、二羧酸代谢通路上；③CHD秽浊痰阻证组与非秽浊痰阻证组尿液中差异表达代谢物主要富集在脂肪酸合成、细胞色素P450对外源性物质的代谢、炎症介质调节等代谢通路上。科学意义：揭示新疆CHD秽浊痰阻证与非秽浊痰阻证代谢相关因素及代谢组学水平上的差异性，并提供各证型所表达的特异性代谢通路，为后续的深入研究奠定基础；阐明地域性因素与新疆CHD特有证型秽浊痰阻证代谢特征的交互影响，为地域性因素对CHD代谢水平的影响提供客观依据。