家兔心脏停搏自主循环恢复后血清代谢组学特征分析  

Serum metabolomic characteristics of rabbits with return of spontaneous circulation after cardiac arrest

作　　者：梁明宇 冯洋 刘娅荣 李淑彤 欧阳洁琳 陈芳[2] 祝益民[2] 邹联洪 蒋宇[2] LIANG Ming-yu;FENG Yang;LIU Ya-rong;LI Shu-tong;OUYANG Jie-lin;CHEN Fang;ZHU Yi-min;ZOU Lian-hong;JIANG Yu(Hunan Normal University,Hunan Provincial Key Laboratory of Molecular Epidemiology,Changsha 410013,China;Institute of Emergency Medicine,Hunan Provincial People's Hospital/the First Affiliated Hospital of Hunan Normal University,Changsha 410005,China)

机构地区：[1]湖南师范大学,分子流行病学湖南省重点实验室,湖南长沙410013 [2]湖南省人民医院(湖南师范大学附属第一医院)湖南省急救医学研究所,湖南长沙410005

出　　处：《中国病理生理杂志》2022年第3期434-441,共8页Chinese Journal of Pathophysiology

基　　金：湖南省重大专项(No.2020SK1010)。

摘　　要：目的:探讨分析家兔心脏停搏(CA)自主循环恢复(ROSC)后血清代谢组学特征变化。方法:10只雄性新西兰家兔,采用窒息法制备CA家兔模型,于CA前、ROSC后15 min、3 h、6 h和24 h各收集2 mL血液样品,通过气相色谱-质谱联用(GC-MS)测定各时间点血清代谢产物,采用Simca P软件对血清代谢轮廓特征进行主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA),通过MetaboAnalyst 5.0软件进行t检验、火山图、聚类热图分析差异代谢产物,并对差异代谢物进行KEGG代谢通路分析。结果:与CA前相比,ROSC后15 min、3 h、6 h和24 h家兔的血清代谢轮廓特征发生明显改变,分别有50、44、58和78个差异代谢物,其中山梨糖、赖氨酸、乙醇胺、2′-脱氧胞苷-5′-三磷酸和腐胺含量在ROSC后均减少(P<0.05),莽草酸、磷酸丝氨酸、N-甲基-L-谷氨酸、4-羟基-3-甲氧基苯甲醇(香草醇)、塔格糖、氨基丙二酸、乳果糖、吲哚-3-乙酸、景天庚酮糖和肌酸含量在ROSC后均增加(P<0.05)。牛磺酸含量在ROSC后15 min、6 h和24 h减少(P<0.05),在ROSC后3 h含量差异无统计学意义。与CA前相比,ROSC后15 min、3 h、6 h和24 h分别有8、8、12和15条差异代谢通路,其中苯丙氨酸、酪氨酸和色氨酸的生物合成在ROSC后均下调,精氨酸和脯氨酸代谢在15 min和3 h时下调,而在6和24 h时上调。磷酸戊糖途径在ROSC后15 min时受到抑制,但是在其他时点无差异。结论:CA家兔ROSC后的血清代谢组学存在显著动态差异。磷酸戊糖途径受限和牛磺酸水平下调可能与ROSC后的损伤有关,而肌酸水平上调提示心肌细胞损伤。AIM:To investigate and analyze the dynamic changes of serum metabolomic characteristics in cardiac arrest(CA)rabbit model with return of spontaneous circulation(ROSC).METHODS:The rabbit model of CA was induced by asphyxiation.Blood samples were collected at different time points including before CA,or 15 min,3 h,6 h and 24 h after ROSC.The metabolites in serum were determined by gas chromatography-mass spectrometer(GC-MS).Simca P software was used to analyze the serum metabolic profile characteristics by principal component analysis(PCA)and orthogonal partial least squares discrimination analysis(OPLS-DA).T-test,volcano plot,cluster heat map analysis and KEGG of MetaboAnalyst 5.0 software were used to analyze the differential metabolites and metabolic pathways.RESULTS:Compared with normal group,the characteristics of serum metabolic profiles at 15 min,3 h,6 h and 24 h after ROSC were significantly changed.There were 50,44,58 and 78 differential metabolites at these four time points.Concentrations of sorbose,lysine,ethanolamine,2′-deoxycytidine 5′-triphosphate and putrescine were down-regulated(P<0.05),while shikimic acid,O-phosphoserine,N-methyl-L-glutamic acid,4-hydroxy-3-methoxybenzyl alcohol,tagatose,aminomalonic acid,lactulose,indole-3-acetic acid,sedoheptulose and creatine were up-regulated(P<0.05).Taurine was decreased at 15 min,6 h and 24 h after ROSC(P<0.05),and was recovered at 3 h after ROSC.Compared with normal group,8,8,12 and 15 differential metabolic pathways were captured at 15 min,3 h,6 h and 24 h after ROSC,respectively.The biosynthesis of phenylalanine,tyrosine and tryptophan was down-regulated after ROSC.The metabolism of arginine and proline was down-regulated at 15 min and 3 h after ROSC,while it was up-regulated at 6 and 24 h after ROSC.Pentose phosphate pathway was inhibited at 15 min after ROSC,but there was no difference at other time points.CONCLUSION:Significant dynamic differences in serum metabolomics were observed after ROSC in CA rabbit model.Restricted pentose phosphate pathway

关 键 词：心脏停搏 自主循环恢复 代谢组学 

分 类 号：R363[医药卫生—病理学] R446[医药卫生—基础医学]