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目的采用核磁(1H-NMR)代谢组学技术初步探讨四氯化碳(CCl4)致大鼠急性肝损伤后血清代谢物变化规律。方法 SD大鼠随机分为空白、模型两组,模型组ip 40%CCl4植物油溶液造成急性肝损伤模型,空白组注射等体积的植物油,造模24 h后股动脉取血,常规肝脏病理切片,取血前12 h禁食不禁水。比色法测定血清丙氨酸氨基转移酶(ALT)含量,600 MHz NMR波谱仪分析血清中小分子代谢物代谢轮廓,并对数据进行多元统计分析。结果模型组中ALT的含量显著升高,肝脏病理切片显示模型组大鼠的肝组织内形成很多空泡,肝细胞变大,坏死严重,有出血和大量中性粒细胞浸润;血清1H-NMR代谢图谱中共鉴定了20个代谢物,并确认了6个与CCl4致肝损伤相关的标志物。结论常规血生化指标和肝病理切片结果与代谢组学的多元统计分析结果相一致,且代谢组学可发现引起肝损伤的代谢标志物。
Objective To investigate the changes of serum metabolites after acute liver injury induced by carbon tetrachloride (CCl4) in rats using 1H-NMR metabolomics. Methods Sprague-Dawley rats were randomly divided into two groups. The model rats were induced with acute liver injury by ip 40% CCl4 vegetable oil solution. The blank rats were injected with equal volume of vegetable oil. Blood was drawn from the femoral artery 24 hours later, Fasting 12 h before fasting can not help but water. Serum alanine aminotransferase (ALT) levels were determined by colorimetric method. The metabolite profile of small-molecule metabolites in serum was analyzed by 600 MHz NMR spectroscopy. Multivariate statistical analysis was performed on the data. Results The content of ALT in the model group was significantly increased. The pathological sections of liver showed that many vacuoles were formed in the liver tissue of rats in the model group. The hepatocytes became larger, with severe necrosis and hemorrhage and a large number of neutrophil infiltration. Serum 1H-NMR A total of 20 metabolites were identified in the metabolic profile and 6 markers associated with CCl4-induced hepatic injury were identified. Conclusion The results of routine blood biochemistry and liver biopsy are consistent with the results of multivariate statistical analysis of metabonomics, and metabolomics can find metabolic markers of hepatic injury.