颅内动脉瘤壁的定量蛋白质组学研究  

Quantitative proteomic analysis of the intracranial aneurysm wall using iTRAQ labeling coupled with2D LC-MS/MS

作　　者：王道奎[1] 王成东[2] 曲秉坤[1] 王喆[1] 鞠吉雨[3] 王玉亭[1] 王增武[1] 闫红梅[1] 曹培成[1] 

机构地区：[1]山东省潍坊市人民医院神经外科,山东省潍坊市261041 [2]山东省潍坊市人民医院产前诊断实验室 [3]山东省潍坊医学院免疫教研室

出　　处：《中华神经外科杂志》2013年第12期1281-1285,共5页Chinese Journal of Neurosurgery

基　　金：山东省科技发展计划项目（2011YD21004）;潍坊市科技发展计划项目（201102007）

摘　　要：目的筛选动脉瘤壁差异表达蛋白质，为动脉瘤形成和破裂的分子机制研究提供思路。方法收集破裂的14例动脉瘤壁标本，以匹配的14例颅脑外伤手术患者颞浅动脉做正常对照，等量混合同组内标本，采用同位素标记的绝对和相对定量技术（iTRAQ）和2D-LC-MS／MS法进行差异蛋白质分析。结果共鉴定出蛋白质915个，其中差异2倍以上的蛋白质有255个，包括102个上调蛋白和153个下调蛋白。上调的蛋白质主要与细胞免疫炎性反应、细胞自噬与凋亡以及细胞黏附迁移等生物过程相关；下调的蛋白质主要与细胞骨架连接、细胞组分形态形成、信号传导和蛋白质转运有关。其中，细胞自噬诱导分子（TM9SFl）和杀青素1（AZUl）上调最高为8．0倍；血管张力纤维形成相关蛋白质（SORBS2）下调最显著为12．1倍。结论破裂动脉瘤壁有多种蛋白质表达异常，其中TM9SFl、AZUl及SORBS2的变化可能参与了动脉瘤破裂的分子机制。Objective To screen the differentially expressed proteins of the intracranial aneurysm wall and provide some clues to the study of molecular mechanisms of its formation and rupture. Methods Aneurysm wall samples were intraoperatively collected from 14 patients underwent microneurosurgical clipping and the matched superficial temporal artery tissues from the patients with head injury were used as the normal control. All vascular tissues in the same group were mixed up by each equal weight（5rag）. The differentially expressed proteins were identified using isobaric tags for relative and absolute quantitation （iTRAQ） coupled with two -dimensional liquid chromatography -tandem mass spectrometry（2D LC - MS/MS）. Results A total of 915 proteins were identified, 255 of which differed more than two -fold in ruptured aneurysm wall tissues compared with the control group, including 102 up - regulated proteins and 153 down -regulated ones. In the up -regulated proteins, there were a number of proteins associated with biological process including immune response, inflammation response, cell motion, cell adhesion, cell apoptosis and autophagy while cell skeleton junction, cell component morphology formation, signaling transduction and protein transport in the down -regulated ones. Transmembrane 9 superfamily member 1 （ TM9SF1, 8.0 fold ） and Azurocidin （ AZU1,8.0 fold ） were markedly increased among the up - regulated proteins. Sorbin and SH3 domain - containing protein 2 （SORBS2,12. 1 fold） was markedly decreased among the down - regulated proteins. Conclusions The results suggest that a number of proteins expressed differently in ruptured aneurysm wall tissues. Major proteins such as TM9SF1, AZU1, and SORBS2, may participate in the molecular mechanisms of aneurysm rupture. This knowledge would be important value for elucidating molecular mechanisms of aneurysm rupture and formation and insight for novel therapeutic strategies to prevent rupture.

关 键 词：颅内动脉瘤 蛋白质组学 同位素标记的绝对和相对定量技术 液质联用 

分 类 号：R739.4[医药卫生—肿瘤]