扩张型心肌病蛋白质组学研究  

Proteomic Study in Patients With Idiopathic Dilated Cardiomyopathy

作　　者：于丽平[1] 史琳影[1] 朱晓明[1] 蔡军[1] 杨新春[1] 孟宪敏 

机构地区：[1]首都医科大学附属北京朝阳医院心脏中心,北京市100020 [2]首都医科大学 [3]阜外心血管病医院

出　　处：《中国循环杂志》2013年第1期47-50,共4页Chinese Circulation Journal

摘　　要：目的:通过蛋白质组学方法比较扩张型心肌病(DCM)患者和正常人心肌组织差异蛋白质谱,找出与DCM相关的差异蛋白,进一步探讨DCM发生的分子生物学机制。方法:选择9例原发病为DCM、左心室射血分数<35%且接受心脏移植手术的患者作为DCM组:心肌组织取自患者自有心脏的左心室游离壁。对照组:心肌组织取自6例不能用作移植的供体心脏。采用双向凝胶电泳(2-DE)分析蛋白质谱差异,热考马斯亮蓝染色,串联质谱(MS-MS)鉴定差异蛋白。采用生物医学研发软件及资料库Ingenuity PathwaysAnalysis分析差异蛋白的定位、功能和相互作用。结果:DCM组和对照组心肌组织2-DE图像中蛋白点的整体分布比较相似,可以检测到超过1 000个蛋白点。通过比较分析,共鉴定出25种差异蛋白,其中在DCM组15种上调,10种下调。使用LOCATE数据库分析差异蛋白的亚细胞定位,提示其中大分子蛋白占40%,细胞骨架蛋白为28%,线粒体蛋白为28%。蛋白的PANTHER分类显示大多数差异蛋白参与了细胞的结构、肌肉收缩、钙离子转运和水解酶的活性等功能。生物学途径分类揭示差异蛋白参与了组织的形成过程、生物调节、发育过程、代谢过程和对刺激的应答过程等。结论:对DCM患者心肌组织蛋白质组学研究发现25种差异蛋白,其中上调表达的蛋白有15种,下调表达的有10种;这些蛋白参与了线粒体能量代谢、心肌收缩、凋亡等过程;提示这些过程可能在DCM发生发展中发挥重要作用。Objective：To compare the differences of protein expression in myocardium between normal subjects and the patients with idi- opathic dilated cardiomyopathy（ DCM）by proteomic study and to explore the molecular basis of DCM. Methods：Our work included 2 groups. DCM group ,n=9 ,the patients＇ left ventricular ejection fraction 〈35% and received heart transplantation,the cardiac tissue for proteomic study taken from the free wall of their own left ventricle. Normal control group, n = 6, the cardiac tissue from unmatched normal donors. The protein spectrum was examine by 2-D electrophoresis, the dif- ferential protein was identified by MS-MS method, and the position, function and interaction of differential proteins were investiga- ted with Ingenuity pathway analysis. Results ：2-D electrophoresis presented similar protein spectrums for a total of 1000 spots in both groups, and the comparative analysis found 25 differential proteins, and 15 of them up-regulated and 10 down-regulated in DCM group. LOCATE database clas- sification for sub cellular localization showed that there were 40% of macromolecular protein, 28% of cytoskeleton protein and 28% of mitocbondrial protein. PANTHER protein itemization indicated that the majority of proteins involved in cell structure, mus- cle contraction, calcium transportation and hydroIase activity. Tbe biological protein category explored that the differential proteinsparticipated in tissue processes, biological regulation, developmental and metabolic processes and the response to stimulus in the body. Conclusion：There were 25 differential proteins involved in mitochondrial metabolism, myocardial contraction and apoptosis, which may play the important role in DCM development and process.

关 键 词：扩张性心肌病 蛋白质组学 能量代谢 

分 类 号：R54[医药卫生—心血管疾病]