冠心病心阳虚痰瘀互结证大鼠模型的代谢组学特征分析  

Analysis on Metabonomic Characteristics of Rat Model of Coronary Heart Disease with Heart Yang Deficiency,Phlegm and Blood Stasis Syndrome

作　　者：赵辉 曹洪欣[1] 李想[2] 吴浩南 李抒凝 唐丹丽[3] 张华敏[5] ZHAO Hui;CAO Hongxin;LI Xiang;WU Haonan;LI Shuning;TANG Danli;ZHANG Huamin(Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Information on Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China;Heilongjiang University of Chinese Medicine,Harbin 150006,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]中国中医科学院中医药信息研究所,北京100700 [3]中国中医科学院医学实验中心,北京100700 [4]黑龙江中医药大学,哈尔滨150006 [5]中国中医科学院中药研究所,北京100700

出　　处：《中国中医基础医学杂志》2023年第5期734-741,共8页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81873199);国家自然科学基金项目(81973722);中国中医科学院中医基础理论研究所自主选题项目(YZ-202215)。

摘　　要：目的 构建冠心病心阳虚痰瘀互结证大鼠模型,阐释其代谢组学特征。方法 采用丙基硫氧嘧啶灌胃联合高脂饮食、腹腔注射维生素D3和皮下注射异丙肾上腺素构建冠心病心阳虚痰瘀互结证模型,通过观察大鼠行为学改变,测定心功能、心电图、耳温、尾静脉脉波、舌象与足底RGB(red,green,blue)值、心肌组织三磷酸腺苷(adenosine triphosphate,ATP)含量、血脂含量、血液流变学指标、炎症因子白细胞介素(interleukin,IL)-6与肿瘤坏死因子(tumor necrosis factor,TNF)-α含量及甲状腺功能指标,结合主动脉弓组织、心肌组织病理改变对该模型进行评价;应用代谢组学技术筛选出冠心病心阳虚痰瘀互结证大鼠差异代谢物,并进行通路富集分析。结果 冠心病心阳虚痰瘀互结证大鼠表现出精神萎靡、行动迟缓、蜷缩扎堆、耳温降低、毛发缺少光泽,舌象、足底色泽偏淡暗伴RGB值升高,左心室射血分数(ejection fraction, EF)、左心室短轴缩短率(fraction shortening, FS)降低,心电图ST段抬高、脉波增宽;血清中总胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、IL-6、TNF-α含量升高, T3、T4及心肌组织中ATP含量降低;主动脉弓平滑肌细胞坏死钙化、心肌组织纤维化坏死溶解。冠心病心阳虚痰瘀互结证组大鼠与空白组大鼠之间共有160个差异代谢物,主要涉及ABC转运器、花生四烯酸代谢、嘧啶代谢、不饱和脂肪酸的生物合成和氨基酸的生物合成等代谢通路。结论 本研究构建了冠心病心阳虚痰瘀互结证大鼠模型,并初步揭示了其代谢特征。Objective To construct a rat model of coronary heart disease with syndrome of heart Yang deficiency,phlegm and blood stasis.Then elucidate its metabonomic characteristics.Methods The animal model of coronary heart disease with syndrome of heart Yang deficiency,phlegm and blood stasis was established by intragastric administration of propylthiouracil combined with a high fat diet,intraperitoneal injection of vitamin D3 and subcutaneous injection of isoproterenol.The rat model was evaluated by observing the behavioral changes,and measuring cardiac function,electrocardiogram,temperature of ear,tail pulse wave,RGB values of tongue and plantar,myocardial ATP content,blood lipid content,hemorheology indicators,inflammatory factors IL-6 and TNF-α,thyroid function and pathological changes of aortic arch and myocardial tissue.Using metabolomics technology to screen out differential metabolites in this model,and perform pathway enrichment analysis.Results The rat of coronary heart disease with syndrome of heart Yang deficiency,phlegm and blood stasis showed listlessness,slow movement,crouching,decreasing ear temperature,lack of hair luster,pale and dark color of tongue and sole image with increased RGB value,decreased EF and FS in cardiac ultrasound,elevated ST segment in ECG,and broadened pulse.The model still showed the contents of TC,LDL-C,IL-6,TNF-αincreased,while T3,T4 and ATP decreased.The pathological results showed the necrosis and calcification of aortic arch,necrosis and dissolution of myocardial tissue.There were 160 different metabolites between the control rats and model rats,which involving ABC transporters,arachidonic acid metabolism,pyrimidine metabolism,unsaturated fatty acid biosynthesis,and amino acid biosynthesis pathway.Conclusion This study established a rat model of coronary heart disease with syndrome of heart Yang deficiency,phlegm and blood stasis,and preliminarily revealed its metabolic characteristics.

关 键 词：冠心病 心阳虚 痰瘀互结 动物模型 代谢组学 

分 类 号：R256.2[医药卫生—中医内科学]