慢性房颤心房肌细胞成分结构的基因本体法分析  

Gene ontology analysis of component structure of atrial muscle cells in patients with chronic atrial fibrillation

作　　者：曾祥君[1] 肖学钧[2] 吴岳恒[2] 黄焕雷[2] ZENG Xiangjun;XIAO Xuejun;WU Yueheng;HUANG Huanlei(Guizhou Provincial People's Hospital, Guiyang 550002, China)

机构地区：[1]贵州省人民医院,贵阳550002 [2]广东省心血管病研究所

出　　处：《山东医药》2019年第7期1-4,9,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81260020);贵州省科学技术基金资助项目(黔科合J字[2009]2165号);贵州省科技攻关项目(黔科合SY字[2010]3089号)

摘　　要：目的应用基因本体法研究慢性房颤心房肌细胞成分分子病理异常。方法选择接受二尖瓣置换术的二尖瓣狭窄为主的48例风湿性心脏病患者,其中慢性房颤24例(慢性房颤组)、窦性心律24例(窦性心律组)。取两组右心耳心肌,采用Western blotting法检测钙调蛋白(CaM)表达,应用全基因组表达谱芯片检测技术,获取数据行主成分、系统聚类及细胞组件基因本体分析。结果慢性房颤组、窦性心律组心房肌组织中CaM相对表达量分别为0.199±0.058、0.135±0.034,两组相比P<0.05。主成分分析显示,慢性房颤组和窦性心律组心房肌样本在二维空间上明确分布于不同的区域;系统聚类将所有样本聚为慢性房颤和窦性心律两类;DIVID系统在线分析显示,慢性房颤和窦性心律差异表达基因在细胞成分本体有肌原纤维、细胞外基质、胶原三聚体等37个注释条目异常;注释条目富集聚类显示,心房肌结构受房颤影响依次为细胞外成分、收缩纤维及细胞骨架等。结论慢性房颤与窦性心律心房肌基因表达模式明显不同,慢性房颤心房肌细胞外结构、收缩纤维、细胞骨架、细胞膜、膜锚蛋白、内质网、线粒体、脂肪及脂蛋白颗粒等细胞成分在分子水平与窦性心律心房肌存在明显异常。Objective To study the atrial molecular pathological change of patients with chronic atrial fibrillation (AF) by gene ontology. Methods We selected 48 rheumatic heart disease patients predominantly with mitral stenosis undergoing mitral valve replacement, including 24 cases with chronic AF (chronic AF group) and 24 cases with sinus rhythm (sinus rhythm group). The calmodulin (CaM) expression was detected by Western blotting. The gene expression profiles of chronic AF were studied by hierarchical clustering and principal component, and the function of differentially expressed genes was analyzed by the software of DIVID. Results The protein expression of CaM was higher in the chronic AF group than in the sinus rhythm group [(0.199±0.058) vs.(0.135±0.034), P <0.05]. The principal component analysis showed that the atrial muscle samples in the chronic AF group and sinus rhythm group were distributed in different regions of two-dimensional space. Significantly regulated genes were enriched in 37 meaning classifications of cellular components by gene ontology, including the extracellular region, cytoplasmic vesicle, myofibril, cytoskeleton, endoplasmic reticulum, mitochondrion, lipid particle,lipoprotein particle and membrane part, and so forth. Annotation clusters of enrichment terms displayed that the cell structure of extracellular matrix, extracellular region, contractile fiber and cytoskeleton were strongly abnormal in turn. Conclusions Atria cells have clearly different gene expression patterns between chronic AF and sinus rhythm patients, and gene ontology analysis shows that the extracellular structure, contractile fiber, cytoskeleton, cell membrane, membrane angioprotein, endoplasmic reticulum, mitochondria, fat and lipoprotein granules of chronic AF have significant abnormalities at the molecular level and sinus rhythm atrial muscle.

关 键 词：慢性房颤 基因表达模式 主成分分析 聚类分析 

分 类 号：R541.7[医药卫生—心血管疾病]