心脏骤停血清代谢组学研究

Study of Serum metabolomics on asphyxiation-induced cardiac arrest

目的基于气相色谱-质谱联用技术(GC-MS)测定心脏骤停家兔血清代谢组学指标,寻找心脏骤停血清差异代谢产物,初步揭示心脏骤停的病理生理变化。方法将2.5kg的雄性新西兰家兔按随机数字表法分为假手术组(n=24)和心脏骤停组(n=24)。采用窒息法制备心脏骤停家兔模型;与心脏骤停前、自主循环恢复后30min,心脏骤停后24h收集动脉血样,进行血气分析和通过GC-MS测定两组血浆中的小分子代谢产物,并对其进行代谢轮廓分析,筛选相关差异代谢产物。结果与正常对照组比,LPS组小鼠血清中炎症因子TNF-和IL-1以及黏附分子ICAM-1,VCAM-1和E-selectin水平明显升高,IL-6变化不明显,肺湿干重比增加,肺组织间隔增宽,炎症细胞浸润。与LPS组相比,葛根素组小鼠血清中炎症因子TNF-和IL-1以及黏附分子ICAM-1,VCAM-1和E-selectin水平明显降低,IL-6变化不明显,肺湿干重比下降,肺组织间隔增宽程度降低,炎症细胞浸润减少。结论用GC-MS检测心脏骤停家兔的血清代谢特征发生明显改变,糖类、脂类、氨基酸、和核酸多种代谢通路发生紊乱。

Objective To determine the cardiac arrest rabbits serum metabolomics by gas chromatography-mass spectrometry (GC-MS), and find the differential metabolites between cardiac arrest group and sham group, and to reveal the pathophysiological changes of cardiac arrest. Methods 2.5Kg male New Zealand rabbits were randomly divided into sham operation group (n=24) and cardiac arrest group (n=24).cardiac arrest was induced by asphyxiation;arterial blood samples were collected before cardiac arrest, 30 minutes after recovery of spontaneous circulation, and 24 hours post cardiac arrest, blood gas analysis and metabonomic were determined by Blood Gas Analyzer and GC-MS respectively.Analyze the metabolic profiling and screen the differential metabolites between CA group and sham group. Results The serum lactate level of rabbits with Asphyxiation-induced cardiac arrest was significantly increased, and the oxygen partial pressure was significantly decreased 24 h after CA.GC-MS screened 351 metabolites, including 41 differential metabolites, 28 up-regulated metabolites, and 13 down-regulated metabolites.PCA analysis show that metabolism characteristics of Asphyxiation-induced cardiac arrest rabbits were significantly changed.Metabolic pathway analysis found that 28 metabolic pathways were disfunction in the cardiac arrest group.β-alanine metabolism, glutamate and proline metabolism, pentose phosphate pathway, glutathione metabolism, histidine metabolism, fructose and mannose metabolism, glycine/serine/threonine metabolism, and tryptophan metabolism Significant changes have occurred During cardiac arrest. Conclusions In cardiac arrest rabbit, the The serum metabolic characteristics of Asphyxiation-induced cardiac arrest rabbits were significantly changed, and the metabolic pathways of carbohydrates, lipids, amino acids, and nucleic acids were disordered.