本文選題：肝硬化　切入點：營養(yǎng)風險　出處：《天津醫(yī)科大學》2017年博士論文

【摘要】：目的:評估乙肝肝硬化患者的營養(yǎng)風險;結合血清學檢查、人體測量學、人體成分分析及代謝組學的方法,綜合評估乙肝肝硬化患者的營養(yǎng)狀態(tài)及代謝特點;通過分析患者及健康對照的血清代謝輪廓的變化,建立代謝模型,并進一步篩選特征性離子,鑒定出小分子代謝物,探討乙肝肝硬化患者營養(yǎng)不良的分子機制及對于營養(yǎng)治療的臨床指導價值。方法:選取天津市第三中心醫(yī)院2014年8月至2015年6月的住院乙肝肝硬化患者83例為研究對象,根據(jù)肝功能Child-Pugh評分對應分為Child-Pugh A、Child-Pugh B及Child-Pugh C三組,以健康體檢者35例為對照組。應用營養(yǎng)風險篩查2002量表(NRS-2002)評估患者的營養(yǎng)風險;測量病例組及對照組的體重指數(shù)(BMI)、肱三頭肌皮褶厚度(TSF)、上臂肌圍(MAMC)及握力(優(yōu)勢手);利用人體成分分析儀(多頻生物電阻抗法,BIA法)分別檢測病例組及對照組的細胞內(nèi)水分(ICW)、細胞外水分(ECW)、身體總水分(TBW)、細胞外水分/總水分比值(ECW/TBW)、蛋白質(zhì)、脂肪、骨骼肌的含量;應用超高效液相色譜與質(zhì)譜聯(lián)用(UPLC-MS)方法對血清樣本進行分析,采用基于模式識別的多元統(tǒng)計分析對數(shù)據(jù)進行處理并對差異性代謝物的變化趨勢進行分析,篩選出特征性小分子代謝物。結果:入院的83例乙肝肝硬化患者經(jīng)NRS-2002量表進行評估,有營養(yǎng)風險的患者占72.3%,其中Child-Pugh A、Child-Pugh B、Child-Pugh C三組中有營養(yǎng)風險患者的比例分別為54.5%、79.3%和90.5%;BMI、MAMC在Child-Pugh A組、B組、C組及對照組之間并無明顯對應關系;TSF及握力在各組之間有統(tǒng)計學差異;ECW/TBW、骨骼肌、體脂肪含量在各組間有統(tǒng)計學差異;同時,握力與Child-Pugh評分及NRS2002評分均呈明顯負相關,而ECW/TBW與Child-Pugh評分呈正相關。應用代謝組學的方法檢測出乙肝肝硬化患者血清中11種小分子代謝物含量較對照組降低(均P0.001),它們分別是:8種溶血磷脂酰膽堿、鳥氨酸、甘油磷酸膽堿、葡萄糖醛酸;2種小分子代謝物即油酰甘油磷酸絲氨酸和牛磺膽酸較對照組升高,(均P0.001)。且8種溶血磷脂酰膽堿、油酰甘油磷酸絲氨酸、鳥氨酸、牛磺膽酸、葡萄糖醛酸、甘油磷酸膽堿含量與Child-Pugh評分均具有相關性。結論:乙肝肝硬化患者營養(yǎng)風險發(fā)生率高,營養(yǎng)不良狀態(tài)普遍存在;TSF、握力、ECW/TBW、骨骼肌、體脂肪含量在評估住院乙肝肝硬化患者的營養(yǎng)狀態(tài)中相對敏感;應用生物電阻抗技術(BIA法)測定人體體成分的變化,在評估乙肝肝硬化患者營養(yǎng)狀態(tài)中可以發(fā)揮重要作用,尤其在肝硬化早期即可發(fā)現(xiàn)細胞內(nèi)外水分、骨骼肌及體脂肪的變化。但在患者出現(xiàn)腹水、水腫等情況下,其應用受到一定限制。乙肝肝硬化患者血清中篩選出有明顯變化的13種特征性小分子代謝物,它們分別參與脂代謝、氨基酸代謝、膽汁酸代謝等多個代謝通路。并隨肝臟代償能力的下降而發(fā)生顯著變化,可從側面反映乙肝肝硬化患者的代謝特點,并為臨床營養(yǎng)治療提供潛在靶點。
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R512.62;R575.2

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