【摘要】：妊娠期糖尿病(Gestational diabetes mellitus,GDM)作為妊娠期間最常見的代謝異常并發(fā)癥,對孕產(chǎn)婦及胎兒均有很大危害,早期發(fā)現(xiàn)、早期控制可有效降低并發(fā)癥的產(chǎn)生,改善妊娠結(jié)局。目前尚缺乏可靠便捷的早期篩查方法,而蛋白質(zhì)組學(xué)是近年來研究蛋白質(zhì)的一個全新的方法,其特點為能夠快速、大規(guī)模、全面的篩選候選蛋白,己成為發(fā)現(xiàn)生物標(biāo)記物的新途徑,但由于其操作復(fù)雜,成本高,臨床應(yīng)用相對較少,目前尚無妊娠糖尿病的尿液蛋白質(zhì)組學(xué)研究報道。本研究采用蛋白質(zhì)組學(xué)方法分析篩查孕婦尿液蛋白,不僅可為篩查尿液生物標(biāo)記物提供基礎(chǔ),建立GDM早期篩查的方法,也可以為進(jìn)一步研究GDM發(fā)病機(jī)理提供實驗依據(jù)。 尿液中的蛋白具有多種功能,蘊(yùn)含豐富信息,且因其無創(chuàng)、便捷的采樣方式而在診斷和篩查中具有優(yōu)勢。近來尿液蛋白質(zhì)組學(xué)領(lǐng)域的研究己揭示了許多疾病相關(guān)的尿液蛋白質(zhì),其中包括2型糖尿病相關(guān)的蛋白質(zhì)。 本研究目的為分別建立孕周為25-30周的正常健康孕婦和GDM孕婦的尿液蛋白質(zhì)譜,并通過比較篩查差異蛋白。采用乙醇沉淀法提取尿液蛋白質(zhì),Bradford法測定濃度,每組納入樣本數(shù)為9例,各組尿液分別混合,經(jīng)微波輔助的蛋白酶裂解,使用液相色譜-質(zhì)譜／質(zhì)譜方法進(jìn)行蛋白質(zhì)鑒定。 本研究在正常健康孕婦尿液中鑒定出837種蛋白,在GDM孕婦尿液中鑒定出791種蛋白,共鑒定出983種蛋白質(zhì)。通過比較兩組區(qū)別,發(fā)現(xiàn)14種差異蛋白,其中GRN、FGB、CPVL、S100A11等在GDM組表達(dá)上調(diào),HSPA8、LTF、CA1等在GDM組表達(dá)下調(diào)。這些蛋白多與葡萄糖代謝相關(guān)。下一步應(yīng)進(jìn)行蛋白質(zhì)驗證、擴(kuò)大樣本量的研究,為臨床提供指導(dǎo)。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R714.256

【共引文獻(xiàn)】

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1 覃保瑜;糖尿病腎病大鼠尿液和腎皮質(zhì)線粒體蛋白質(zhì)組學(xué)研究[D];廣西醫(yī)科大學(xué);2011年

相關(guān)碩士學(xué)位論文 前8條

1 吳菁;尿液蛋白質(zhì)質(zhì)譜分析在2型糖尿病腎病中的應(yīng)用[D];浙江大學(xué);2011年

2 方樂;尿AAG檢測在T2DM患者糖尿病腎病早期診斷中的應(yīng)用研究[D];南昌大學(xué);2012年

3 陳月梅;β_2-微球蛋白檢測試劑的研發(fā)及臨床應(yīng)用[D];中南大學(xué);2012年

4 曹潔;匹伐他汀與阿托伐他汀對急性冠脈綜合征患者糖代謝影響的對比研究[D];河北醫(yī)科大學(xué);2013年

5 瞿華;2型糖尿病及肥胖患者血漿顆粒蛋白前體水平及其在胰島素抵抗中的作用[D];重慶醫(yī)科大學(xué);2013年

6 王晴;IgA腎病氣陰兩虛證的血清蛋白組學(xué)研究[D];福建中醫(yī)藥大學(xué);2014年

7 羅蘭英;原發(fā)性肝癌組織間質(zhì)液中肝癌相關(guān)蛋白的鑒定及初步驗證[D];廣西醫(yī)科大學(xué);2014年

8 高漫云;血清顆粒蛋白前體與肥胖、2型糖尿病的相關(guān)性[D];蘇州大學(xué);2014年

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本文編號：2400468