本文關鍵詞： 嬰兒巨細胞病毒肝炎 脾虛濕困證 代謝組學 氣相色譜質(zhì)譜聯(lián)用　出處：《南京中醫(yī)藥大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:研究巨細胞病毒(Cytomegalovirus,CMV)肝炎脾虛濕困證患兒血漿和尿液的代謝特征、受干擾的代謝物和代謝通路,探討CMV肝炎脾虛濕困證的證候?qū)嵸|(zhì)。方法:選取符合診斷標準的CMV肝炎脾虛濕困證患兒20例設為脾虛濕困組。同時選取同時期同年齡段正常兒童20例設為正常組。采集兩組兒童的血漿和尿液,應用氣相色譜-三重四級桿質(zhì)譜儀(gas chromatography-mass spectrometry,GC-MS)檢測代謝產(chǎn)物,利用 XCMS軟件進行數(shù)據(jù)提取和數(shù)據(jù)轉(zhuǎn)化,導入SIMCA-P軟件進行多變量分析,并建立主成分分析(Principal Component Analysis,PCA)和正交偏最小二乘法判別分析(Orthogonal Partial Least Squares Discriminant Analysis,OPLS-DA)數(shù)學模型,篩選能有效表征嬰兒 CMV 肝炎脾虛濕困證的差異性代謝物,并使用MetaboAnalyst分析可能涉及的相關代謝通路來綜合評價CMV肝炎脾虛濕困證的證候本質(zhì)。結(jié)果:1.血漿樣本代謝組學模式分析結(jié)果顯示,在所構(gòu)建的PCA及OPLS-DA模型中正常組血漿樣本提取物與嬰兒CMV肝炎脾虛濕困證組樣本能夠良好區(qū)分,說明脾虛濕困證組的代謝物特征與正常組具有明顯差異。初步鑒定了 22個差異性代謝物作為潛在的生物標記物,其中乳酸、L-丙氨酸、辛酸、L-異亮氨酸、L-脯氨酸、甘氨酸、絲氨酸、L-蘇氨酸、氨基丙二酸、蛋氨酸、焦谷氨酸、戊酸、L-谷氨酸、鳥氨酸、L-賴氨酸、L-酪氨酸、肌醇、硬脂酸、L-色氨酸和膽固醇在CMV肝炎脾虛濕困證患兒血漿中呈上調(diào)趨勢,而3-羥基丁酸、乙二胺四乙酸在CMV肝炎脾虛濕困證患兒血漿中呈下調(diào)趨勢。2.尿液樣本代謝組學模式分析結(jié)果顯示,在所構(gòu)建的PCA及OPLS-DA模型中正常組尿液樣本提取物與嬰兒CMV肝炎脾虛濕困證組樣本能夠良好區(qū)分,說明脾虛濕困證組的代謝物特征與正常組具有明顯差異。初步鑒定了 9個差異性代謝物作為潛在的生物標記物,其中甘氨酸、L-蘇氨酸、L-賴氨酸、D-甘露醇、D-葡萄糖酸、棕櫚酸、尿酸、硬脂酸在CMV肝炎脾虛濕困證患兒尿液中呈上調(diào)趨勢,而檸檬酸在CMV肝炎脾虛濕困證患兒尿液中呈下調(diào)趨勢。結(jié)論:1.本實驗所采用的GC-MS技術能夠?qū)MV肝炎患兒的血漿、尿液進行代謝輪廓分析,并且能夠區(qū)分和闡釋脾虛濕困證組與正常組不同的代謝特征。2.CMV肝炎脾虛濕困證患兒血漿和尿液中主要存在氨基酸代謝及能量代謝紊亂,涉及以下代謝通路,即甘氨酸、絲氨酸和蘇氨酸代謝;精氨酸和脯氨酸代謝;丙氨酸、天冬氨酸和谷氨酸代謝;氨酰tRNA合成;賴氨酸降解;丙酮酸代謝;磷酸肌醇代謝;谷氨酰胺和谷氨酸代謝;色氨酸代謝;賴氨酸合成。3.本研究篩選出的差異性代謝物有可能是表征嬰兒CMV肝炎脾虛濕困證的潛在的生物標志物。
[Abstract]:Objective: to study the metabolic characteristics of plasma and urine in children with cytomegalovirus cytomegalovirus (CMV) hepatitis due to spleen deficiency and dampness. To explore the syndromes essence of spleen deficiency and dampness in CMV hepatitis. Methods: 20 cases of CMV hepatitis with spleen deficiency dampness were selected as the group of spleen deficiency dampness and 20 cases of normal children of the same age were selected as normal group at the same time. To collect plasma and urine from two groups of children, Gas chromatography-quadruple bar mass spectrometer (chromatography-mass spectrometrymetric GC-MS) was used to detect the metabolites. The data were extracted and transformed by XCMS software, and then imported into SIMCA-P software for multivariate analysis. The mathematical models of principal component analysis (PCA) and orthogonal Partial Least Squares Discriminant analysis (OPLS-DAA) were established. The related metabolic pathways involved in MetaboAnalyst analysis were used to evaluate the syndromes essence of spleen deficiency and dampness in patients with CMV hepatitis. Results: 1.The results of plasma sample metabonomics analysis showed that, In the constructed PCA and OPLS-DA model, the samples of normal group and infant group of CMV hepatitis with spleen deficiency and dampness could be distinguished well. 22 different metabolites were identified as potential biomarkers, including lactic acid L-alanine, octanoic acid L-isoleucine, L-proline, glycine. Serine L-threonine, aminomalonic acid, methionine, pyroglutamic acid, valerate L-glutamic acid, ornithine L-lysine L-tyrosine, inositol, stearic acid L-tryptophan and cholesterol showed an upward trend in the plasma of children with CMV hepatitis due to spleen deficiency. However, the plasma levels of 3-hydroxybutyric acid and ethylenediamine tetraacetic acid were down-regulated in children with CMV hepatitis due to spleen deficiency and dampness. In the constructed PCA and OPLS-DA model, the urine samples of normal group could be distinguished from those of CMV hepatitis group with dampness and dampness syndrome of spleen deficiency in infantile hepatitis. 9 different metabolites were identified as potential biomarkers, among them, glycine L-threonine, L-lysine, D-mannitol, D-gluconic acid and palmitic acid. Uric acid and stearic acid were up-regulated in the urine of children with spleen deficiency and dampness of CMV hepatitis, while citric acid was down-regulated in the urine of children with CMV hepatitis. Conclusion: 1. The GC-MS technique used in this study can be used to treat the plasma of children with CMV hepatitis. Urine metabolism profile analysis, and can distinguish and explain the spleen deficiency dampness trapped syndrome group and normal group of different metabolic characteristics. 2. CMV hepatitis spleen deficiency dampness trapped children plasma and urine mainly exist amino acid metabolism and energy metabolism disorders. Related to the following metabolic pathways: glycine, serine and threonine metabolism; arginine and proline metabolism; alanine, aspartic acid and glutamate metabolism; tRNA synthesis; lysine degradation; pyruvate metabolism; inositol phosphate metabolism; Glutamine and glutamate metabolism; tryptophan metabolism; lysine synthesis. The differential metabolites screened in this study may be a potential biomarker to characterize spleen deficiency and dampness in infants with CMV hepatitis.
【學位授予單位】：南京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R272

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