基于中心碳代谢分析技术的肝胆系统疾病靶向代谢组学研究
投稿时间:2023-02-22  修订日期:2023-11-29  点此下载全文
引用本文:徐圣弢,吴琼,刘佃花,王琳召,谭蔚锋,陈俊.基于中心碳代谢分析技术的肝胆系统疾病靶向代谢组学研究[J].药学实践杂志,2023,41(12):753~759
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作者单位E-mail
徐圣弢 海军军医大学附属东方肝胆外科医院药剂科, 上海 200438  
吴琼 南部战区总医院药剂科, 广东 广州 510010  
刘佃花 上海交通大学医学院附属仁济医院宝山分院, 上海 200444  
王琳召 青岛滨海学院附属医院, 山东 青岛 266000  
谭蔚锋 同济大学附属同济医院肝胆外科中心, 上海 200065 twf1231@163.com 
陈俊 上海交通大学医学院附属仁济医院宝山分院, 上海 200444 chenjuntcdj@126.com 
基金项目:上海市科学技术委员会科研计划项目课题(10495810400);上海市卫生局青年科研基金(2009Y065)
中文摘要:目的 采用超高效液相色谱三重四级杆质谱技术(UPLC-QQQ-MS)对肝胆疾病患者血浆样本内源性中心碳代谢相关化学成分进行分析,寻找肝胆系统病变的可能特征代谢物及显著改变的代谢通路。方法 招募健康志愿者32人、胆管囊肿患者23人、胆道结石患者19人、肝癌患者45人及肝门部胆管癌患者50人,采集血浆样本,进行UPLC-QQQ-MS分析,采用MPP软件进行统计分析,结合模式识别分析各组间代谢组差异,研究肝胆疾病显著改变代谢通路及可能致病机制。结果 代谢组学分析得到胆管囊肿患者15个、胆道结石患者7个、肝癌患者7个和肝门部胆管癌患者3个与健康人血浆中存在显著性差异的可能生物标志物,并分别富集胆管囊肿患者8条、胆道结石患者4条、肝癌4条和肝门部胆管癌患者1条在体内显著改变的代谢通路。结论 根据上述鉴别的差异代谢物和富集的代谢通路结果,表明肝脏病变主要影响了机体的能量代谢及氨基酸的代谢与运输,而磷酸肌醇代谢在胆管囊肿、胆道结石、肝癌和肝门部胆管癌中均显著改变。
中文关键词:中心碳代谢  代谢靶标分析  胆管囊肿  肝癌  肝门部胆管癌
 
Serum metabolomics study on benign liver lesions and hepatic malignancies by central carbon pathway metabolites
Abstract:Objective To screen potential metabolites and significantly altered metabolic pathways of liver lesions by central carbon pathway metabolites. Methods 32 healthy volunteers (HC), 23 patients with biliary cysts (CYST), 19 patients with biliary stones (Stone), 45 patients with hepatocellular carcinoma (HCC), and 50 patients with hilarcholangiocarcinoma (HCCA) were recruited. Their serum samples were collected for UPLC-QQQ-MS analysis and further MPP statistical analysis. Pattern recognition was further used to discovery the differences in metabolome between groups, and to explore the significantly altered metabolic pathway and possible pathogenic mechanism of liver diseases. Results A total of 15, 7, 7, and 3 metabolites and a total of 8, 4, 4, and 1 metabolic pathway that were significantly different in serum between CYST, Stone, HCC, HCCA and healthy controls were identified and enriched through serum metabolomics analysis, respectively. Conclusion According to the above identified differential metabolites and enriched metabolic pathway results, it is shown that liver lesions mainly involved in the energy metabolism and amino acid metabolism & transport, in addition, inositol phosphate metabolism were significantly changed both in CYST, Stone, HCC and HCCA.
keywords:UPLC-QQQ-MS  metabolic target analysis  biliary cyst  liver cancer  hilar cholangiocarcinoma
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