乙肝肝硬化患者的营养状态及血清代谢组学的初步研究

发布时间：2018-04-09 07:03

本文选题：肝硬化　切入点：营养风险　出处：《天津医科大学》2017年博士论文

【摘要】：目的:评估乙肝肝硬化患者的营养风险;结合血清学检查、人体测量学、人体成分分析及代谢组学的方法,综合评估乙肝肝硬化患者的营养状态及代谢特点;通过分析患者及健康对照的血清代谢轮廓的变化,建立代谢模型,并进一步筛选特征性离子,鉴定出小分子代谢物,探讨乙肝肝硬化患者营养不良的分子机制及对于营养治疗的临床指导价值。方法:选取天津市第三中心医院2014年8月至2015年6月的住院乙肝肝硬化患者83例为研究对象,根据肝功能Child-Pugh评分对应分为Child-Pugh A、Child-Pugh B及Child-Pugh C三组,以健康体检者35例为对照组。应用营养风险筛查2002量表(NRS-2002)评估患者的营养风险;测量病例组及对照组的体重指数(BMI)、肱三头肌皮褶厚度(TSF)、上臂肌围(MAMC)及握力(优势手);利用人体成分分析仪(多频生物电阻抗法,BIA法)分别检测病例组及对照组的细胞内水分(ICW)、细胞外水分(ECW)、身体总水分(TBW)、细胞外水分/总水分比值(ECW/TBW)、蛋白质、脂肪、骨骼肌的含量;应用超高效液相色谱与质谱联用(UPLC-MS)方法对血清样本进行分析,采用基于模式识别的多元统计分析对数据进行处理并对差异性代谢物的变化趋势进行分析,筛选出特征性小分子代谢物。结果:入院的83例乙肝肝硬化患者经NRS-2002量表进行评估,有营养风险的患者占72.3%,其中Child-Pugh A、Child-Pugh B、Child-Pugh C三组中有营养风险患者的比例分别为54.5%、79.3%和90.5%;BMI、MAMC在Child-Pugh A组、B组、C组及对照组之间并无明显对应关系;TSF及握力在各组之间有统计学差异;ECW/TBW、骨骼肌、体脂肪含量在各组间有统计学差异;同时,握力与Child-Pugh评分及NRS2002评分均呈明显负相关,而ECW/TBW与Child-Pugh评分呈正相关。应用代谢组学的方法检测出乙肝肝硬化患者血清中11种小分子代谢物含量较对照组降低(均P0.001),它们分别是:8种溶血磷脂酰胆碱、鸟氨酸、甘油磷酸胆碱、葡萄糖醛酸;2种小分子代谢物即油酰甘油磷酸丝氨酸和牛磺胆酸较对照组升高,(均P0.001)。且8种溶血磷脂酰胆碱、油酰甘油磷酸丝氨酸、鸟氨酸、牛磺胆酸、葡萄糖醛酸、甘油磷酸胆碱含量与Child-Pugh评分均具有相关性。结论:乙肝肝硬化患者营养风险发生率高,营养不良状态普遍存在;TSF、握力、ECW/TBW、骨骼肌、体脂肪含量在评估住院乙肝肝硬化患者的营养状态中相对敏感;应用生物电阻抗技术(BIA法)测定人体体成分的变化,在评估乙肝肝硬化患者营养状态中可以发挥重要作用,尤其在肝硬化早期即可发现细胞内外水分、骨骼肌及体脂肪的变化。但在患者出现腹水、水肿等情况下,其应用受到一定限制。乙肝肝硬化患者血清中筛选出有明显变化的13种特征性小分子代谢物,它们分别参与脂代谢、氨基酸代谢、胆汁酸代谢等多个代谢通路。并随肝脏代偿能力的下降而发生显著变化,可从侧面反映乙肝肝硬化患者的代谢特点,并为临床营养治疗提供潜在靶点。
[Abstract]:Objective: to evaluate the nutritional status and metabolic characteristics of patients with hepatitis B cirrhosis by means of serological examination, anthropometry, human component analysis and metabolomics.By analyzing the changes of serum metabolic profile in patients and healthy controls, a metabolic model was established, and characteristic ions were further screened to identify small molecular metabolites.To explore the molecular mechanism of malnutrition in patients with liver cirrhosis and its clinical value in nutritional therapy.Methods: 83 patients with hepatitis B cirrhosis in Tianjin third Central Hospital from August 2014 to June 2015 were selected. According to the Child-Pugh score of liver function, 83 patients were divided into three groups: Child-Pugh Agna Child-Pugh B and Child-Pugh C, and 35 healthy persons as control group.The nutritional risk of patients was evaluated by the nutritional risk screening scale 2002 (NRS-2002).The body mass index (BMI), triceps skinfold thickness (TSF), upper arm muscle circumference (MAMCs) and grip strength (dominant hand) were measured in the case group and control group, and the patient group and the control group were detected by human component analyzer (multifrequency bioelectrical impedance method BIA method).ICWN, ECW, TBWN, ECW / TBWN, protein.The content of fat and skeletal muscle; using UPLC-MS to analyze serum samples, processing the data by multivariate statistical analysis based on pattern recognition, and analyzing the trend of variation of metabolites.The characteristic small molecule metabolites were screened out.Results: 83 patients with hepatitis B cirrhosis were assessed by NRS-2002 scale.At the same time, the grip strength was negatively correlated with Child-Pugh score and NRS2002 score, while ECW/TBW was positively correlated with Child-Pugh score.The contents of 11 small molecule metabolites in serum of patients with liver cirrhosis were lower than those of the control group (P 0.001). They were: 1: 8 kinds of lysophosphatidylcholine, ornithine, choline glycerophosphate.Two small metabolites of glucuronide, namely oleyl glycerophosphate serine and taurocholic acid, were higher than those of the control group (P 0.001).The levels of lysophosphatidylcholine, oleyl glycerophosphate serine, ornithine, taurocholic acid, glucuronic acid, choline glycerophosphate were correlated with Child-Pugh score.Conclusion: the incidence of nutritional risk in patients with hepatitis B cirrhosis is high, the prevalence of malnutrition is TSF, grip strength ECW / TBW, skeletal muscle, body fat content is relatively sensitive in evaluating the nutritional status of hospitalized patients with liver cirrhosis.The determination of body composition by bioelectric impedance technique (BIA) can play an important role in evaluating the nutritional status of patients with hepatitis B cirrhosis, especially in the early stage of cirrhosis, the changes of intracellular moisture, skeletal muscle and body fat can be detected.However, in patients with ascites, edema and other cases, its application is limited.Thirteen kinds of characteristic small molecule metabolites were screened out from the serum of patients with hepatitis B cirrhosis, which were involved in lipid metabolism, amino acid metabolism, bile acid metabolism and other metabolic pathways.It can reflect the metabolic characteristics of patients with liver cirrhosis and provide potential targets for clinical nutrition therapy.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R512.62;R575.2

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