冠心病心血瘀阻证大鼠心肌组织代谢组学研究  

Study on Metabonomics of Myocardial Tissue of Rat Model with Coronary Heart Disease of Heart Blood Stasis Syndrome

作　　者：李静[1,2] 郭志华[1,2] 刘建和[3] 钟森杰 匡慧芳 杨漾 刘祎 张秋雁[1] LI Jing;GUO Zhihua;LIU Jianhe;ZHONG Senjie;KUANG Huifang;YANG Yang;LIU Yi;ZHANG Qiuyan(Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Key Laboratory of Colleges and Universities of Intelligent Traditional Chinese Medicine Diagnosis and Preventive Treatment of Chronic Diseases of Hunan University of Chinese Medicine,Changsha 410208,China;The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南中医药大学慢病中医智能诊断与治未病湖南省普通高等学校重点实验室,湖南长沙410208 [3]湖南中医药大学第一附属医院,湖南长沙410007 [4]广州中医药大学第一附属医院,广东广州510405

出　　处：《中国中医药信息杂志》2024年第3期119-126,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81574039、82174343);湖南省教育厅重点项目(21A0253);湖南中医药大学学科建设“揭榜挂帅”项目(22JBZ005);湖南中医药大学研究生创新项目(2022CX04);中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(21PTKF1012)。

摘　　要：目的研究冠心病心血瘀阻证大鼠心肌组织代谢产物谱,探讨其病证生物学基础。方法SD大鼠随机分为假手术组和模型组,采用冠状动脉左前降支结扎法制备冠心病心血瘀阻证大鼠模型,观察大鼠一般状态,检测舌象色度、心电图、心功能,HE染色、透射电镜观察心肌组织形态及超微结构,用超高效液相色谱-质谱技术检测心肌组织差异代谢物,并对代谢通路进行富集分析。结果与假手术组比较,模型组大鼠舌象色度R、G、B值均显著降低(P<0.05),心电图心率、ST段抬高幅度显著上升(P<0.05),左室射血分数、左室短轴缩短率显著下降(P<0.05),左室收缩末期内径、左室舒张末期内径显著上升(P<0.05);心肌组织结构模糊,有炎性细胞浸润,线粒体肿胀、破裂、溶解,嵴结构断裂减少。代谢组学共鉴定出29个假手术组与模型组差异显著的潜在生物标志物(7个上调、22个下调),主要富集于硫胺素代谢,精氨酸生物合成,嘌呤代谢,氨酰基-tRNA生物合成,丙氨酸、天冬氨酸和谷氨酸代谢,戊糖和葡萄糖醛酸相互转化,糖酵解/糖异生,缬氨酸、亮氨酸和异亮氨酸降解,三羧酸循环,丙酮酸代谢10条代谢通路。结论冠状动脉左前降支结扎法可较好地模拟冠心病心血瘀证病理过程,其病理机制涉及葡萄糖代谢、线粒体能量代谢、氨基酸代谢、蛋白质生物合成、嘌呤代谢等多层次代谢网络紊乱。Objective To investigate the biological basis of disease and syndrome by studying the spectrum of myocardial tissue metabolites in the rat model of coronary heart disease with heart blood stasis syndrome.Methods SD rats were randomly divided into sham-operation group and model group.The left anterior descending coronary artery was ligated to prepare the rat model of coronary heart disease with heart blood stasis syndrome.The general condition was observed,and the tongue chromaticity,electrocardiogram,cardiac function were detected.HE staining and transmission electron microscopy were used to observe myocardial tissue morphology and ultrastructure.UPLC-MS technology was used to investigate the differential metabolites in rat myocardial tissue,and enrichment analysis was conducted on metabolic pathways.Results Compared with the sham-operation group,the tongue chromaticity R,G,B values of model group rats were significantly reduced(P<0.05),ECG heart rate and ST segment elevation amplitude significantly increased(P<0.05),LVEF and LVFS significantly decreased,and LVIDs and LVIDd significantly increased(P<0.05).Myocardial tissue pathology revealed that the structure was blurred,inflammatory cells infiltrated,mitochondria swelled,ruptured,and dissolved,and crista structure fracture decreased.A total of 29 potential biomarkers with significant differences between the sham-operation group and the model group were identified in metabolomics(7 upregulated and 22 downregulated),with the majority of 10 pathways enriched in thiamine metabolism,arginine biosynthesis,purine metabolism,aminoacyl-tRNA biosynthesis,alanine,aspartate and glutamate metabolism,pentose and glucuronate interconversions,glycolysis/gluconeogenesis,valine,leucine and isoleucine degradation,TCA cycle,pyruvate metabolism.Conclusion Ligation of the left anterior descending coronary artery can mimic the pathological process of coronary heart disease with blood stasis syndrome in a good way,and its pathological mechanism involves the disruption of multi-level m

关 键 词：冠心病 心血瘀阻证 生物学基础 代谢组学 大鼠 

分 类 号：R285.5[医药卫生—中药学]