肝损伤代谢组学模型的构建及其中药提取物水飞蓟宾治疗的评价  

Establishment of Metabonomics Model of Liver Injury and the Model-based Evaluation of Treatment with Silybin

作　　者：钱婷婷 朱旭婷[2,3] 卢吟秋 李依桐 喻春皓 谢洪平[2] QIAN Tingting;ZHU Xuting;LU Yinqiu;LI Yitong;YU Chunhao;XIE Hongping(Department of Pharmaceutical Engineering,Huaiyin Institute of Technology,Huai’an223000;College of Pharmaceutical Sciences,Soochow University,Suzhou215123;Affiliated Hospital of Jiangnan University,Wuxi 214000)

机构地区：[1]淮阴工学院制药工程系,江苏淮安223000 [2]苏州大学医学部药学院,江苏苏州215123 [3]江南大学附属医院,江苏无锡214000

出　　处：《分析科学学报》2021年第5期581-586,共6页Journal of Analytical Science

摘　　要：利用四氯化碳致肝损伤动物模型,以尿液为样本,采用构建的色谱基线漂移和外源性代谢物信号消除的方法,获得了内源性代谢物总离子流色谱,建立了肝损伤代谢组学模型,该模型表达的四氯化碳致毒特征与组织细胞显微特征和血清学指标一致。当模型动物给予水飞蓟宾治疗时,治疗前的代谢组学分类特征与模型组一致,治疗后与正常对照组一致;代谢组学表征的“治疗后肝损伤回调”特征与肝组织显微成像特征一致,然而血清学指标虽然也明显回调,但还未回调到与正常对照组一致。由此表明,代谢组学疗效评价的灵敏性与“损伤性”的作为“金标准”的组织显微成像一致,而明显高于常规血清学检测。建立的代谢组学模型实现了非损伤、准确、灵敏的中药治疗评价。An LC-MS/MS approach has been developed for the detection of urine as the metabolic sample from CCl4 induced liver injury rats,and the two-dimensional matrix data of the samples were obtained.The total ion chromatograms of endogenous metabolites were obtained by using the constructed eliminating methods based on the selectivity and orthogonality of mass spectra for the shift of chromatogram baseline and the signals of exogenous metabolites.The total ion chromatograms were used to characterize metabolic profiles,and the metabonomics model of liver injury was established.The CCl4-induced toxic characteristics expressed in the model were consistent with the microscopic characteristics of liver tissues and cells and the serological indexes.Silybin,a Chinese herbal extract,was used to treat the liver injury,and the metabonomics behavior before and after treatment was studied by using the metabonomics model.The results showed that the metabonomics behavior after treatment had an obvious going-back trend to the normal control group.The classification characteristics before treatment were consistent with the model group.After treatment,they were consistent with the normal control group,and the liver tissue microscopic imaging characteristics were also gone back to the same as the normal control group.The serum markers also significantly went back,but it has not yet returned to the normal state.The results showed that the sensitivity of the metabonomic model based treatment evaluation for liver injury was consistent with that of the"invasive"tissue microscopic imaging as"gold standard",and significantly higher than that of the conventional detection of serum markers.Therefore,the obtained chromatograms of endogenous metabolites accurately characterizes the toxicological state and pathological state,and the established metabonomics model realizes the non-invasive,accurate,sensitive,convenient and continuous evaluation for traditional Chinese medicine treatment.

关 键 词：内源性代谢物谱 代谢组学 治疗评价 水飞蓟宾 中药提取物 肝损伤 

分 类 号：O657.63[理学—分析化学]