兔体外循环模型心肌代谢组学研究  

The myocardial metabolic profiling of extracorporeal circulation based on gas chromatography-mass spectrometry in a rabbit model

作　　者：邹丽华 刘晋萍[2] Zou Lihua;Liu Jinping(Department of Anesthesiology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Extracoporeal Circulation,Fuwai Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China)

机构地区：[1]首都医科大学附属北京天坛医院麻醉科,北京100070 [2]北京协和医学院,中国医学科学院,阜外心血管病医院体外循环科,北京100037

出　　处：《中国体外循环杂志》2021年第4期228-234,共7页Chinese Journal of Extracorporeal Circulation

基　　金：国家自然科学基金(81670375);院所青年基金(2017-YQN-11)。

摘　　要：目的利用代谢组学探讨兔体外循环(ECC)期间心肌代谢变化。方法18只新西兰白兔随机分为对照组(C组,n=6)、缺血组(I组,n=6)、缺血再灌注组(IR组,n=6)。I组与IR组行右腋动脉、右房插管建立ECC,I组主动脉阻断120 min后取左室心肌组织;IR组主动脉阻断120 min开放,心肌恢复灌注120 min后取左室心肌组织;C组正中开胸、右腋动脉、右房插管后取左室心肌组织。采用气相色谱-质谱法检测,代谢组学数据进行多元变量统计分析:主成分分析、正交偏最小二乘法-判别分析(OPLS-DA)作得分图,差异物质鉴定采用OPLS-DA分析的变量重要性投影(VIP)值与独立样本t检验P<0.05,代谢物行载荷图、热力图分析,并进行差异物代谢通路分析。结果缺血期间代谢差异不显著(Q2Y=0.357),13个代谢物质存在统计学差异(所有VIP差异物>1,P差异物<0.05),主要涉及鸟氨酸循环及嘧啶代谢通路。再灌注期间,心肌代谢发生显著变化(Q2Y=0.714),82个代谢物质存在统计学差异(所有差异代谢物VIP值>1,P差异物<0.05),不饱和脂肪酸及其衍生物代谢(花生四烯酸、油酸、亚油酸、茉莉酸甲酯)上调,与黄嘌呤氧化酶系统相关的产物次黄嘌呤、黄嘌呤核苷均增加,腺苷相关代谢产物及三羧酸循环琥珀酸及其代谢产物下调。结论基于兔ECC灌注HTK液模型的代谢组学分析表明缺血期间心肌代谢变化不显著,但再灌注期间心肌代谢显著上调,参与氧化应激的氨基酸、不饱和脂肪酸、嘌呤代谢明显增加,抗氧化剂谷氨酰胺生成减少。Objective To compare the myocardium metabolics profile in a rabbit extracorporeal circulation(ECC)model.Methods 18 New Zealand white rabbits were randomly assigned into control group(C group,n=6),ischemia group(I group,n=6),and ischemia reperfusion group(IR group,n=6).Both groups I and IR were conducted by cannulation on the right atrium and right axillary artery,then aortic root was clamped and cardioplegia arrest was performed by HTK solution perfusion after ECC initiation.Rabbits in group I were sacrificed after aortic root was clamped for 120 min.Myocardial tissue of group IR was obtained after aortic root was clamped for 120 min and de-clamped for 120 min.Control group received median thoracotomy,then intubation in right atrium and right axillary artery were performed.The myocardial tissue was obtained for metabolic analysis later.The metabolic features were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry.Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites,and then t test was applied to test for statistical significance.Results There was no significant difference between group I and group C(Q2Y=0.357).The myocardial metabolic profiling was distinctive significantly between groups IR and I(Q2Y=0.714 for OPLS-DA models),and 82 definable metabolites varied significantly after ECC(all VIP>1,and P<0.05).Several up-regulated amino acids were involved in oxidative stress,including serine,glycine,proline and threonine,whereas the antioxidant glutamine was decreased.The metabolism of unsaturated fatty acids and their derivatives(arachidonic acid,oleic acid,linoleic acid,methyl jasmonate)was up-regulated.Both hypoxanthine and xanthine nucleoside relating to xanthine oxidase system were increased.Adenosine related metabolites and succinic acid in tricarboxylic acid cycle were down-regulated.Conclusion The changes in myocardial metabolism were not significant during ischemia period.Amino acid was significantly up-regula

关 键 词：体外循环 代谢组学 心肌缺血再灌注 兔 

分 类 号：R459.7[医药卫生—急诊医学]