CAJ | 학술논문

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(TM9SF1)和杀青素1(AZU1)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TM9SF1、AZU1及SORBS2的变化可能参与了动脉瘤破裂的分子机制.
목적 사선동맥류벽차이표체단백질,위동맥류형성화파렬적분자궤제연구제공사로.방법 수집파렬적14례동맥류벽표본,이필배적14례로뇌외상수술환자섭천동맥주정상대조,등량혼합동조내표본,채용동위소표기적절대화상대정량기술(iTRAQ)화2D-LC-MS/MS법진행차이단백질분석.결과 공감정출단백질915개,기중차이2배이상적단백질유255개,포괄102개상조단백화153개하조단백.상조적단백질주요여세포면역염성반응、세포자서여조망이급세포점부천이등생물과정상관;하조적단백질주요여세포골가련접、세포조분형태형성、신호전도화단백질전운유관.기중,세포자서유도분자(TM9SF1)화살청소1(AZU1)상조최고위8.0배;혈관장력섬유형성상관단백질(SORBS2)하조최현저위12.1배.결론 파렬동맥류벽유다충단백질표체이상,기중TM9SF1、AZU1급SORBS2적변화가능삼여료동맥류파렬적분자궤제.
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(5mg).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.