【摘要】 目的应用代谢组学技术研究延龄草提取物对非酒精性脂肪肝(NAFLD)大鼠肝脏代谢的影响,探讨延龄草干预NAFLD的作用机制。方法腹腔注射四氯化碳溶液结合复合高脂饮食建立NAFLD大鼠模型,并随机分为正常组、模型组、延龄草提取物高、中、低剂量组,灌胃4周后逆转录聚合酶链反应法(RT-PCR)检测肝细胞能量代谢调节相关基因的表达,应用生化气相色谱-质谱联用技术和模式识别及多元统计分析方法考察延龄草对NAFLD大鼠肝脏代谢组学的影响。结果与模型组比较,延龄草提取物各剂量组大鼠肝细胞低密度脂蛋白受体(LDLR)、解偶联蛋白1(UCP-1)基因表达不同程度升高(P<0.01),脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶1(ACC1)基因表达不同程度下降(P<0.01),OPLS-DA结果显示延龄草能明显降低非酒精性脂肪肝模型大鼠尿液中的苹果酸、柠檬酸、延胡索酸、甘氨酸、缬氨酸和软脂酸甘油脂的含量;升高丁酸、棕榈酸、花生四烯酸和十六碳烯酸,差异均有统计学意义(P<0.05或P<0.01);结论延龄草提取物可能通过调节肝细胞能量代谢相关基因的表达发挥抗非酒精性脂肪肝的作用,并由此导致肝脏代谢物酶谱的变化。更多还原

【Abstract】 Objective To observe the effect of Trillium extract on hepatic metabolism of rats with Nonalcoholic fatty liver disease( NAFLD) by metabonomics technology,and make clear the mechanism of Trillium on NAFLD.Methods The carbon tetrachloride solution was injected into the abdominal cavity and the rats were fed with compound high fat diet to establish NAFLD rat models.The rats were randomly divided into Normal group,Model group,Trillium extract high,middle and low dose groups. Four weeks after gavage,RT-PCR was used to detect the expression of genes related to energy metabolism regulation in hepatocytes.The effects of Trilliums on hepatic metabolism in NAFLD rats were observed by Derivatization Gas Chromatography-Mass Spectrometry,Pattern Recognition and Multivariate Statistical Analysis. Results Compared with the Model group,the gene expression of LDLR and UCP-1 of rats in all Trillium extract groups with different dose increased in different degrees( P<0.01),while the genes expression of FAS and ACC1 decreased in different degrees( P<0.01).The results of OPLS-DA showed that Trillium extract can significantly reduce the content of urine malic acid,citric acid,fumaric acid,glycine,valine and palmitic acid glycerides of nonalcoholic fatty liver rat model and increase butyric acid,palmitic acid,arachidonic acid and palmitoleic acid. The difference was statistically significant( P < 0. 05 or P < 0. 01). Conclusion Trillium extract may play a role in anti nonalcoholic fatty liver by regulating the expression of gene related to energy metabolism of liver cells,which leads to the change of hepatic metabolite profile.更多还原