大鼠非酒精性脂肪肝肝郁脾虚证的尿液代谢组学研究
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摘要
目的:运用核磁共振(nuclear magnetic resonance,1H-NMR)寻找非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)肝郁脾虚证大鼠尿液的内源性代谢产物。方法:复制雄性SD大鼠NAFLD肝郁脾虚证模型,检测血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)及肝匀浆内甘油三酯(triglyceride,TG)和总胆固醇(total cholesterol,TC)含量,观察肝组织病理学特点,1H-NMR检测大鼠尿液的代谢产物变化,运用多元统计分析方法寻找差异性代谢产物。结果:模型组大鼠血清ALT、肝匀浆内TG、TC含量均明显升高,大鼠尿液中找到26种代谢产物,其中发现乙酸、肌酐、二甲胺、甘油、甘氨酸、α-D-葡萄糖、异亮氨酸、α-酮戊二酸、乳酸、亮氨酸、琥珀酸、牛磺酸等12种差异代谢物。结论:通过寻找NAFLD肝郁脾虚证大鼠尿液中内源性代谢产物,为NAFLD肝郁脾虚证的发病机制及临床诊断研究提供实验依据。
Objective: Using the 1 H-NMR technology to search for the endogenous differential metabolic markers in urine of rats with liver depression spleen deficiency of nonalcoholic fatty liver disease( NAFLD). Methods: Establish the male SD rats models of the liver depression spleen deficiency of NAFLD,serum alanine aminotransferase( ALT) and triglyceride( TG) and total cholesterol( TC) in liver homogenate were detected,and the histopathological characteristics of liver tissue were observed.1 H-NMR was used to detect the changes of metabolites in urine of rats,and the multivariate statistical analysis method was used to find the differential metabolic markers. Results: The levels of serum ALT and TG and TC in liver homogenate of model group increased significantly. There were 26 metabolites were found in the urine in model rats. Among these metabolites,12 differential metabolic markers were found. Including acetate,creatinine,Dimethylamine,glycerol,glycine,α-D-glucose,isoleucine,α-ketoglutaric acid,Lactate,leucine,Succinate,taurine. Conclusion: The changes of endogenous metabolic markers can provide experimental evidence for the pathogenesis and clinical diagnosis of NAFLD with liver depression spleen deficiency.
Objective: Using the 1 H-NMR technology to search for the endogenous differential metabolic markers in urine of rats with liver depression spleen deficiency of nonalcoholic fatty liver disease( NAFLD). Methods: Establish the male SD rats models of the liver depression spleen deficiency of NAFLD,serum alanine aminotransferase( ALT) and triglyceride( TG) and total cholesterol( TC) in liver homogenate were detected,and the histopathological characteristics of liver tissue were observed.1 H-NMR was used to detect the changes of metabolites in urine of rats,and the multivariate statistical analysis method was used to find the differential metabolic markers. Results: The levels of serum ALT and TG and TC in liver homogenate of model group increased significantly. There were 26 metabolites were found in the urine in model rats. Among these metabolites,12 differential metabolic markers were found. Including acetate,creatinine,Dimethylamine,glycerol,glycine,α-D-glucose,isoleucine,α-ketoglutaric acid,Lactate,leucine,Succinate,taurine. Conclusion: The changes of endogenous metabolic markers can provide experimental evidence for the pathogenesis and clinical diagnosis of NAFLD with liver depression spleen deficiency.
引文
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[3]苗宇船,刘杨,李若瑜,等.大鼠非酒精性脂肪性肝炎肝郁脾虚证模型的建立[J].世界中西医结合杂志,2018,13(4):1-5.
[4]孙晓倩,孙蓉.大鼠脂肪肝肝郁脾虚证的模型[J].中国实验方剂学杂志,2017,23(10):92-98.
[5]耿放,张宁,方衡,等.逍遥散对急性肝损伤大鼠模型保护作用的代谢组学研究[J].中药材,2014,37(2):275-279.
[6]李若瑜,苗宇船,苏赵威,等.基于1H-NMR技术寻找非酒精性脂肪肝肝郁脾虚证的差异代谢标志物[J].中国中医基础医学杂志,2018,24(3):334-336.
[7]马欣,顾宏图,赵瑜,等.不同证候的非酒精性脂肪肝合并肝损伤患者的血清代谢组学分析[J].中华中医药杂志,2017,32(3):1246-1250.
[8]WEI DD,WANG JS,WANG PR,et al. Toxic effects of chronic low-dose exposure of thioacetamide on rats based on NMR metabolic profiling[J].J pharm Biomed Anal,2014,98(9):334-338.
[9]张治国.乙酸调节脂代谢及乙酸、醋粉预防胰岛素抵抗研究[D].杭州:浙江大学,2008:27-28.
[10]张艳花,王东琴,李小伟,等.基于1H-NMR代谢组学技术寻找CCl4致大鼠急性肝损伤的代谢标志物[J].药物评价研究,2014,37(1):11-16.
[11]何莉莎,顾成娟,崔亚珊,等.仝小林教授从“土壅木郁”辨治代谢综合征经验[J].世界中医药,2015,10(12):1914-1917.
[12]SHALITIN S,BATTELINO T,MORENO LA,et al. Obesity,metabolic syndrome and nutrition nonalcoholic fatty liver disease:lipids and insulin resistance[J]. World Rev Nutr Diet,2016,114(2):21-49.