妊娠期糖尿病患者尿液蛋白质组学研究
发布时间：2019-01-04 15:26
【摘要】：妊娠期糖尿病(Gestational diabetes mellitus,GDM)作为妊娠期间最常见的代谢异常并发症,对孕产妇及胎儿均有很大危害,早期发现、早期控制可有效降低并发症的产生,改善妊娠结局。目前尚缺乏可靠便捷的早期筛查方法,而蛋白质组学是近年来研究蛋白质的一个全新的方法,其特点为能够快速、大规模、全面的筛选候选蛋白,己成为发现生物标记物的新途径,但由于其操作复杂,成本高,临床应用相对较少,目前尚无妊娠糖尿病的尿液蛋白质组学研究报道。本研究采用蛋白质组学方法分析筛查孕妇尿液蛋白,不仅可为筛查尿液生物标记物提供基础,建立GDM早期筛查的方法,也可以为进一步研究GDM发病机理提供实验依据。 尿液中的蛋白具有多种功能,蕴含丰富信息,且因其无创、便捷的采样方式而在诊断和筛查中具有优势。近来尿液蛋白质组学领域的研究己揭示了许多疾病相关的尿液蛋白质,其中包括2型糖尿病相关的蛋白质。 本研究目的为分别建立孕周为25-30周的正常健康孕妇和GDM孕妇的尿液蛋白质谱,并通过比较筛查差异蛋白。采用乙醇沉淀法提取尿液蛋白质,Bradford法测定浓度,每组纳入样本数为9例,各组尿液分别混合,经微波辅助的蛋白酶裂解,使用液相色谱-质谱／质谱方法进行蛋白质鉴定。 本研究在正常健康孕妇尿液中鉴定出837种蛋白,在GDM孕妇尿液中鉴定出791种蛋白,共鉴定出983种蛋白质。通过比较两组区别,发现14种差异蛋白,其中GRN、FGB、CPVL、S100A11等在GDM组表达上调,HSPA8、LTF、CA1等在GDM组表达下调。这些蛋白多与葡萄糖代谢相关。下一步应进行蛋白质验证、扩大样本量的研究,为临床提供指导。
[Abstract]:Gestational diabetes mellitus (Gestational diabetes mellitus,GDM), as the most common metabolic complication during pregnancy, is harmful to both pregnant women and fetuses. Early control can effectively reduce the occurrence of complications and improve the outcome of pregnancy. There is a lack of reliable and convenient early screening methods, and proteomics is a new method for protein research in recent years, characterized by the ability to screen candidate proteins quickly, on a large scale and across the board. It has become a new way to find biomarkers, but because of its complex operation, high cost and relatively few clinical applications, there is no report on urine proteomics of gestational diabetes mellitus. In this study, proteomics was used to analyze and screen urine proteins of pregnant women, which not only provided the basis for screening urine biomarkers, but also provided experimental basis for the early screening of GDM and the further study of the pathogenesis of GDM. Urine proteins have many functions, contain abundant information, and have advantages in diagnosis and screening because of their noninvasive and convenient sampling methods. Recent studies in urine proteomics have revealed many disease-related proteins, including those related to type 2 diabetes. The aim of this study was to establish urine protein profiles of normal pregnant women aged 25 to 30 weeks and pregnant women with GDM, and to screen differentially expressed proteins. Urine protein was extracted by ethanol precipitation method. The concentration of urine protein was determined by Bradford method. Nine samples were included in each group. The urine of each group was mixed separately. The protein was identified by liquid chromatography-mass spectrometry (LC-MS) / mass spectrometry (LC-MS / MS) after microwave-assisted proteolysis. In this study, 837 proteins were identified in the urine of normal pregnant women, 791 proteins were identified in the urine of pregnant women with GDM, and a total of 983 proteins were identified. By comparing the two groups, 14 differentially expressed proteins were found, in which GRN,FGB,CPVL,S100A11 was up-regulated in GDM group and HSPA8,LTF,CA1 was down-regulated in GDM group. Most of these proteins are related to glucose metabolism. The next step should be to carry out protein verification, expand the study of sample size, and provide guidance for clinical practice.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R714.256
本文编号：2400468
[Abstract]:Gestational diabetes mellitus (Gestational diabetes mellitus,GDM), as the most common metabolic complication during pregnancy, is harmful to both pregnant women and fetuses. Early control can effectively reduce the occurrence of complications and improve the outcome of pregnancy. There is a lack of reliable and convenient early screening methods, and proteomics is a new method for protein research in recent years, characterized by the ability to screen candidate proteins quickly, on a large scale and across the board. It has become a new way to find biomarkers, but because of its complex operation, high cost and relatively few clinical applications, there is no report on urine proteomics of gestational diabetes mellitus. In this study, proteomics was used to analyze and screen urine proteins of pregnant women, which not only provided the basis for screening urine biomarkers, but also provided experimental basis for the early screening of GDM and the further study of the pathogenesis of GDM. Urine proteins have many functions, contain abundant information, and have advantages in diagnosis and screening because of their noninvasive and convenient sampling methods. Recent studies in urine proteomics have revealed many disease-related proteins, including those related to type 2 diabetes. The aim of this study was to establish urine protein profiles of normal pregnant women aged 25 to 30 weeks and pregnant women with GDM, and to screen differentially expressed proteins. Urine protein was extracted by ethanol precipitation method. The concentration of urine protein was determined by Bradford method. Nine samples were included in each group. The urine of each group was mixed separately. The protein was identified by liquid chromatography-mass spectrometry (LC-MS) / mass spectrometry (LC-MS / MS) after microwave-assisted proteolysis. In this study, 837 proteins were identified in the urine of normal pregnant women, 791 proteins were identified in the urine of pregnant women with GDM, and a total of 983 proteins were identified. By comparing the two groups, 14 differentially expressed proteins were found, in which GRN,FGB,CPVL,S100A11 was up-regulated in GDM group and HSPA8,LTF,CA1 was down-regulated in GDM group. Most of these proteins are related to glucose metabolism. The next step should be to carry out protein verification, expand the study of sample size, and provide guidance for clinical practice.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R714.256
【共引文献】
相关博士学位论文 前1条
1 覃保瑜;糖尿病肾病大鼠尿液和肾皮质线粒体蛋白质组学研究[D];广西医科大学;2011年
相关硕士学位论文 前8条
1 吴菁;尿液蛋白质质谱分析在2型糖尿病肾病中的应用[D];浙江大学;2011年
2 方乐;尿AAG检测在T2DM患者糖尿病肾病早期诊断中的应用研究[D];南昌大学;2012年
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4 曹洁;匹伐他汀与阿托伐他汀对急性冠脉综合征患者糖代谢影响的对比研究[D];河北医科大学;2013年
5 瞿华;2型糖尿病及肥胖患者血浆颗粒蛋白前体水平及其在胰岛素抵抗中的作用[D];重庆医科大学;2013年
6 王晴;IgA肾病气阴两虚证的血清蛋白组学研究[D];福建中医药大学;2014年
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8 高漫云;血清颗粒蛋白前体与肥胖、2型糖尿病的相关性[D];苏州大学;2014年
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