新生儿脐带血与成人静脉血中性粒细胞生物学过程差异的定量蛋白质组学研究

发布时间：2018-10-16 21:21

【摘要】：目的：新生儿中性粒细胞由于其杀菌机制不成熟导致新生儿高死亡率。新生儿中性粒细胞功能的研究说明新生儿中性粒细胞存在多方面功能不成熟,但是没有一个统一的理论来解释这种功能上的差异。本研究利用定量蛋白质组学技术寻找新生儿和成人中性粒细胞的蛋白质表达差异,从而解释新生儿中性粒细胞功能不成熟的原因。方法：iTRAQ定量蛋白质组学分析两组临床样本：新生儿脐带血和健康成人静脉血。KEGG分析差异蛋白的功能。Western blot用于认证iTRAQ的蛋白表达结果。结果：共有1332个蛋白被检测到,其中98%蛋白被定量。当把差异表达蛋白倍数设定为1.24时,127个蛋白在新生儿和成人中性粒细胞中存在差异(P0.05)。其中103个蛋白表达下调,24个蛋白表达上调,KEGG分别对上调和下调的蛋白进行归类,共有5组被归类,其中4组与免疫相关。这些免疫相关途径包括了蛋白酶体,白细胞跨内皮转移,溶酶体,以及乙醛酸和二羧酸代谢。此外NETs成分在新生儿中性粒细胞中呈现下调表达。结论：我们的研究提供了一个整体的新生儿中性粒细胞与成人中性粒细胞的蛋白表达差异的全貌,揭示了脐带血中性粒细胞的多种功能缺陷。此外,脐带血新生儿NETs组份的下降有可能是NETs在脐带血中性粒细胞中形成推迟的原因。
[Abstract]:Objective: Neonatal neutrophilic granulocytes due to its immature sterilization mechanism led to high neonatal mortality. The study of neutrophil function shows that neutrophil is immature in many ways, but there is no unified theory to explain the functional difference of neonate neutrophil. In this study, quantitative proteomics was used to find the difference of protein expression between neonate and adult neutrophils, so as to explain the immature function of neutrophil. Methods: iTRAQ quantitative proteomics analysis of two groups of clinical samples: neonatal umbilical cord blood and healthy adult venous blood KEGG analysis of differential protein functional. Western blot used to verify the results of iTRAQ protein expression. Results: a total of 1332 proteins were detected, of which 98% were quantified. When the multiple of differentially expressed protein was set to 1.24, 127 proteins were different in neonate and adult neutrophils (P0.05). Among them, 103 proteins were down-regulated and 24 proteins were up-regulated. KEGG classified the up-regulated and down-regulated proteins into 5 groups, 4 of which were immune-related. These immune-related pathways include proteasome, leukocyte transendothelial metastasis, lysosome, and glyoxylic acid and dicarboxylic acid metabolism. In addition, the expression of NETs was down-regulated in neutrophilic granulocytes. Conclusion: our study provides a complete picture of the difference in protein expression between neutrophils and adult neutrophils and reveals the multiple functional defects of neutrophils in umbilical cord blood. In addition, the decrease of NETs component in umbilical cord blood neonates may be the reason for the delayed formation of NETs in cord blood neutrophilic granulocytes.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R722.1

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