乙肝肝硬化伴前肌少症患者的代谢组学双平台研究  

Dual metabolic platform to analyze differential metabolites in hepatitis B virus-related liver cirrhosis patients with pre-sarcopenia

作　　者：刘雪纯 关鸽[2] 张景利[3] 宋广辉[4] 牛庆慧[2] 赵建建 张凌云[1] 荆雪[1] Liu Xuechun;Guan Ge;Zhang Jingli;Song Guanghui;Niu Qinghui;Zhao Jianjian;Zhang Lingyun;Jing Xue(Department of Gastroenterology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China;Liver Disease Center,The Affiliated Hospital of Qingdao University,Qingdao 266003,China;Radiology Department,The Affiliated Hospital of Qingdao University,Qingdao 266003,China;Department of clinical laboratory,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院消化内科,266003 [2]青岛大学附属医院肝病中心,266003 [3]青岛大学附属医院放射科,266003 [4]青岛大学附属医院检验科,266003

出　　处：《中华临床营养杂志》2023年第6期343-353,共11页Chinese Journal of Clinical Nutrition

基　　金：山东省自然科学基金委员会(ZR2021MH209)。

摘　　要：目的通过代谢组学双平台分析,揭示乙型肝炎(简称乙肝)肝硬化伴前肌少症患者的代谢特征,识别潜在的生物标志物,为营养支持治疗提供方向。方法征集青岛大学附属医院乙肝肝硬化住院患者的临床资料和血样本。通过CT测量第三腰椎横截面的骨骼肌面积,计算骨骼肌指数。前肌少症的诊断标准:男性骨骼肌指数<46.96,女性骨骼肌指数<32.46。最终纳入15例乙肝肝硬化伴前肌少症的患者和14例乙肝肝硬化非前肌少症的患者。通过液相色谱-质谱和气相色谱-质谱对血浆进行代谢组学分析。结果液相色谱-质谱和气相色谱-质谱分别富集到5种和28种差异代谢通路,其中氨基酸相关的代谢通路、尿素循环通路、乙醛酸盐和二羧酸盐代谢通路与乙肝肝硬化肌肉质量减少相关。3-羟基丙醛、苯丙酸、甜菜碱醛、(r)-3-羟基丁酸、磷酸羟基丙酮酸和肌酐的曲线下面积大于0.7,可以作为乙肝肝硬化伴肌肉重量减少的潜在生物标志物。结论研究筛选出33条紊乱的代谢通路和多种差异代谢物,绝大多数紊乱的代谢通路与氨基酸代谢、尿素循环和乙醛酸盐和二羧酸盐代谢通路有关。对乙肝肝硬化患者进行差异代谢物筛选,可以尽早识别前肌少症,开展营养干预,延缓疾病进展,改善预后。Objective This study aimed to analyze differential metabolites in patients using a dual metabolic platform and to orientate early nutritional intervention in patients with cirrhosis.Methods The skeletal muscle index(SMI)was calculated based on computed tomography(CT)measurements of skeletal muscle cross-sectional area at the third lumbar vertebra level.Pre-sarcopenia was diagnosed for males with SMI<46.96 and for females with SMI<32.46.Fifteen HBV-related liver cirrhosis patients with pre-sarcopenia were included as Group S while fourteen liver cirrhosis without pre-sarcopenia were Group NS.Liquid chromatography-mass spectrometry(LC-MS)and gas chromatography-mass spectrometry(GC-MS)analyses were used to detect differential metabolites and disturbed pathways in the two groups.Results Five pathways and twenty-eight pathways were defined as disturbed pathways in the plasma of liver cirrhosis patients with pre-sarcopenia by LC-MS and GC-MS,respectively.Most of these pathways are related to amino acid metabolism.Forty-two differential metabolites were imported into the disturbed pathways.Moreover,3-hydroxypropanal,hydrocinnamic acid,betaine aldehyde,phosphohydroxypyruvic acid,(r)-3-hydroxybutyric acid,and creatinine were identified as potential biomarkers for pre-sarcopenia in HBV-related liver cirrhosis.Conclusions The study identified a total of 33 pathways and related differential metabolites that were disturbed in HBV-related liver cirrhosis with pre-sarcopenia.The amino acid metabolism,urea cycle,and glyoxylate and dicarboxylate metabolism pathways may be associated with pre-sarcopenia in patients with HBV-related liver cirrhosis.These results provide a direction for nutritional supplementation in liver cirrhosis.

关 键 词：乙肝肝硬化 前肌少症 差异代谢物 氨基酸代谢 尿素循环 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]