摘要
目的基于超高效液相色谱-飞行时间质谱(UPLC-QTOF-MS)技术寻找CA后大鼠心肌损伤的潜在生物标志物,初步揭示亚低温对心肌保护作用的机制。方法建立窒息性CA模型,将20只自主循环恢复后的SD大鼠随机分为常温组、亚低温组,ROSC后24h收集心肌组织样本进行代谢组学检测,采用SIMCA-P 14.1和MetaboAnalyst 4.0对预处理后的数据进行代谢轮廓分析,筛选差异代谢物,将内源性代谢物进行代谢通路分析。结果成功制作了大鼠窒息性CA模型,心肌HE染色显示,常温组大鼠心肌结构紊乱,心肌纤维断裂,间质充血,细胞核染色不均匀,亚低温治疗后改善了心肌损伤程度;代谢组学检测结果显示,常温组和亚低温组心肌代谢指纹不同,共筛选出20种差异代谢物,代谢通路分析提示嘌呤代谢、缬氨酸/亮氨酸/异亮氨酸代谢在亚低温干预后显著改变。结论亚低温治疗在一定程度上减轻CA后心肌损伤程度,嘌呤代谢和氨基酸代谢参与了亚低温对心肌的保护。
Objective To find potential biomarkers of myocardial injury in rats after CPR based on ultra high performance liquid chromatography-time of flight mass spectrometry(UPLC-QTOFMS)technology,and to reveal the mechanism of mild hypothermia on myocardial protection.Methods CA model was induced by asphyxia.Twenty SD rats recovered from spontaneous circulation were randomly divided into normal temperature group and mild hypothermia group.Myocardial tissue samples were collected 24 hours after ROSC for metabolomics detection.SIMCA-P 14.1 and MetaboAnalyst 4.0 were used to analyse metabolic profile,differential metabolites,and metabolic pathway.Results A model of asphyxiated rat CA was successfully produced.Myocardial HE staining showed that myocardial structure disorder,myocardial fiber rupture,interstitial congestion,and uneven nuclear staining in the normal temperature group.The myocardial injury induced by CA was improved after mild hypothermia treatment.Metabolomics analysis showed that the myocardial metabolic fingerprints between the normal temperature group and the mild hypothermia group were significantly different,and a total of 20 differential metabolites were screened.Metabolic pathways analysis showed that purine metabolism,valine/leucine/isoleucine metabolism were significant after mild hypothermia intervention.change.Conclusions Mild hypothermia can alleviate the degree of myocardial injury after CPR.Purine metabolism and amino acid metabolism involved in the mild hypothermia protection for CA induced myocardial injury.
作者
周靓
唐轶珣
徐一笑
韩小彤
祝益民
Zhou Liang;Tang Yiyi;Xu Yixiao;Han Xiaotong;Zhu Yimin(The First Affiliated Hospital of Hunan Normal University/Hunan Provincial People’s Hospital,Changsha,China;Hunan Provincial Institute of Emergency Medicine,Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics,Changsha,China;Emergency Department,Hunan Provincial People’s Hospital,Changsha,China)
基金
湖南省自然科学基金项目(项目编号:2017JJ2153)。
