基于代谢组学探讨理脾调脂胶囊改善高脂血症大鼠脂代谢紊乱的作用机制

Discussing the Mechanism of Lipi Tiaozhi Capsule on Improving Lipid Metabolism Disorder in Hyperlipidemic Rats Based on Metabonomics

目的:利用代谢组学的策略和方法,通过研究理脾调脂胶囊对高脂血症大鼠模型脂代谢的影响,探讨理脾调脂胶囊对调控脂代谢的作用机制。方法:将大鼠随机分为正常组、模型组与理脾调脂胶囊实验组,对模型组与实验组采用脂肪乳灌胃的方法复制高脂血症大鼠模型,造模成功后对理脾调脂胶囊实验组大鼠灌理脾调脂胶囊药液进行干预,28天后腹主动脉取血,采集血清样本,利用全自动生化分析仪检测血脂水平;采用UPLC-Q-TOF-MS对不同组别的血清样本进行检测,运用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)筛选正常组、模型组和理脾调脂胶囊实验组之间的差异代谢物,利用质谱信息和公共数据库检索对差异代谢物进行鉴定并进行KEGG代谢通路分析。结果:宏观药学显示模型组大鼠血脂水平明显升高,理脾调脂胶囊实验组大鼠血脂水平明显降低,接近正常组;代谢组学研究发现三组大鼠的血清脂质质谱分离良好,并鉴定出与高脂血症相关的肌酸、肌酐、柠檬酸、异柠檬酸、亮氨酸、异亮氨酸、尿酸、缬氨酸等8个潜在生物标志物,涉及的代谢通路包括氨基酸代谢、三羧酸循环、嘌呤代谢等。结论:理脾调脂胶囊对高脂血症脂代谢紊乱大鼠体内的差异代谢物有一定的回调作用,其主要作用机制与调节三羧酸循环,改善氨基酸代谢以及嘌呤代谢密切相关。

Objective:Using metabolomics strategies and methods, by studying the effect of Lipi Tiaozhi Capsule on lipid metabolism in hyperlipidemia rat model, to explore the mechanism of Lipi Tiaozhi Capsule on regulating lipid metabolism. Methods:Rats were randomly divided into normal group, model group and experimental group of Lipi Tiaozhi Capsule. The rats in the model group and the experimental group with stomach perfusion of fat emulsion to replicate the hyperlipidemia rat model. After successful modeling, the rats were randomly divided into normal group, model group and experimental group of Lipi Tiaozhi Capsule. Subsequently, the rats in the experimental group of Lipi Tiaozhi Capsule were perfused with Lipi Tiaozhi Capsule. After 28 days, blood samples were collected from abdominal aorta and blood lipid levels were detected by automatic biochemical analyzer. UPLC-Q-TOF-MS was used to detect serum samples from different groups. Principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to screen metabolites among the normal group, the model group and the experimental group of Lipi Tiaozhi Capsule. Using mass spectrometry and public database retrieval to identify differential metabolites, and analyzing KEGG metabolic pathways. Results:The macroscopic pharmacy showed that the level of serum lipids in the model group increased significantly, and that in the experimental group of Lipi Tiaozhi Capsule decreased significantly, which was close to the normal group. Metabolomics study found that the serum lipid mass spectrometry of the three groups of rats was well separated, and identified eight potential biomarkers associated with hyperlipidemia, creatine, creatinine, citric acid, isocitrate, leucine, isoleucine, uric acid, and valine. The metabolic pathways include three carboxylic acid cycle, amino acid metabolism, purine metabolism and so on. Conclusion:Lipi Tiaozhi Capsule has a certain effect on the differential metabolites in rats with hyperlipidemia and lipid metabolism disorder. The main mechanism is closely related to the regulation of tricarboxylic acid cycle, improvement of amino acid metabolism and purine metabolism.