赶黄草总黄酮对酒精性脂肪肝小鼠肝保护作用的代谢组学研究

Metabolomics Study on the Liver Protection Effect of Total Flavone Extract from Penthorum Chinense Pursh on Alcoholic Fatty Liver in Mice

关键词:  赶黄草  酒精性脂肪肝  代谢组学  UPLC-Q/TOF-MS

Key words:  Penthorum chinense Pursh  alcoholic fatty liver  metabolomics  UPLC-Q/TOF-MS

摘要:

目的 利用代谢组学技术寻找赶黄草总黄酮对酒精性脂肪肝小鼠保护作用的生物标志物。方法 采用5%酒精的Lieber-Decarli液体饲料建立酒精性脂肪肝小鼠模型，观察其肝组织病理形态，测定小鼠血清中ALT、AST、GSH等生化指标水平，并采用UPLC-Q/TOF-MS代谢组学技术，结合偏最小二乘法和正交校正的偏最小二乘法筛选赶黄草总黄酮治疗酒精性脂肪肝的相关生物标志物，揭示赶黄草的保肝作用及其主要代谢途径。结果 赶黄草能显著降低酒精性脂肪肝小鼠血清中ALT、AST水平，升高GSH的含量，改善其脂肪肝变性和炎症。代谢组学分析表明，赶黄草可逆转酒精性肝损伤小鼠血清中4-乙酰氨基丁酸酯、9-顺-视黄醇、油酰胺、taxa-4（20），11（12）-dien-5alpha-yl acetate、3alpha，12alpha-dihydroxy-5beta-chol-6-enoate和鞘氨醇的水平异常；代谢通路分析表明，赶黄草对酒精性脂肪肝的保护作用主要与调控鞘脂代谢通路有关。结论 本研究初步揭示赶黄草可能通过调控鞘脂代谢而起到治疗酒精性脂肪肝的作用。

Abstract:

OBJECTIVE To explore the biomarkers for the protective effect of total flavones of Penthorum chinense Pursh(PCP) on alcoholic fatty liver in mice by using metabolomics technology. METHODS Alcoholic fatty liver mouse model was established by using 5% alcohol of Lieber-Decarli liquid feed. Observing the pathological slices liver tissue in mice, and determining biochemical index levels of mice serum including ALT, AST and GSH, and using the UPLC-Q/TOF-MS metabolomics technology, combined with partial least squares discrimination analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) methods to screening biomarkers related to alcoholic liver injury that treated by PCP, reveal out the function of PCP protecting liver and its metabolic pathways. RESULTS PCP could significantly reduce the levels of ALT, AST and increase the content of GSH in the serum of alcoholic fatty liver mice, and improve fatty liver degeneration and inflammation. Metabolomics analysis showed that PCP could regulate the abnormal level of 4-acetamidobutanoate, 9-cis-retinol, oleamide, Taxa-4(20),11(12)-dien-5alpha-yl acetate, 3alpha,12alpha-dihydroxy-5beta- chol-6-enoate and sphinganine in the serum of alcoholic fatty liver mice. Through the analysis of metabolic pathway, the protective effect of PCP on alcoholic fatty liver was mainly related to the regulation of sphingolipid metabolism pathway. CONCLUSION This study preliminarily reveale that PCP may play a role in the treatment of alcoholic fatty liver by regulating sphingolipid metabolism.