激活乙酰胆碱作用靶标对血管内皮细胞基因表达的影响  

The gene expression profiles through activating endothelial target for acetylcholine

作　　者：陈冬梅[1] 汪海[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学通报》2004年第12期1346-1352,共7页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展规划资助项目 ;NoG19980 5 1112 ;北京赛德维康医药研究院新药研究基金资助项目;No 19990 0 1

摘　　要：目的　研究激活乙酰胆碱作用靶标 (ETA)对血管内皮细胞基因表达的影响。方法　采用人类cDNA表达谱芯片 ,比较氨甲酰胆碱和毛果芸香碱对人冠脉内皮细胞基因表达的影响及其生物学功能。结果　既激活ETA又激活M受体的氨甲酰胆碱 ,以及仅激活M受体的毛果芸香碱 ,在 10 0μmol·L-1浓度下与内皮细胞共孵育 10h ,以含有 14 0 0 0条人类unigene的BiostarH 14 112ScDNA表达谱芯片检测内皮细胞基因表达的变化 ,发现差异基因共 80 1条。两药共同诱导的差异基因 4 91条 ,上调 2 0 5条 ,下调 2 86条。两药诱导差异基因存在很大差别 ,其中氨甲酰胆碱诱导上调基因 119条 ,下调基因 191条 ,这些差异基因均不受毛果芸香碱的影响。进一步分析氨甲酰胆碱特异性诱导差异基因的功能 ,发现有受体与G蛋白、离子通道、血栓、动脉粥样硬化相关基因等七大类。结论　氨甲酰胆碱特异性诱导的差异基因与ETA及其效应器系统以及激活ETA产生抗动脉粥样硬化和抗血栓的分子机制相关。Aim To investigate the effects of gene expression through activating endothelial target for acetylcholine (ETA).Methods Comparative studies were carried out to explore the distinct gene expression of carbachol and pilocarpine.Results Human coronary aortic endothelial cells were incubated with carbachol which activates ETA and muscarinic receptors and with pilocarpine which activates muscarinic receptors distinctly for 10 hours at the concentration of 100 μmol·L -1.The endothelial gene expression was detected by BiostarH-14112S cDNA expression profiling microarrays containing 14 000 human unigenes. There were 801 differential genes totally (491 differentially expressed both by carbachol and by pilocarpine, 310 differentially expressed by carbachol exclusively). We found a significant increase in expression of 119 and a significant decrease in expression of 191 genes after treatment by carbachol preferentially. And these genes were not affected by pilocarpine. Further globally functional catagorization indicates that there are seven types of distinct expressed genes induced by carbachol selectively including membrane receptors and G proteins, ion channels, G protein coupled receptors, transcriptional factors, apoptosis-related genes, cell adhesive factors, thrombosis and atherosclerosis-related genes.Conclusion The differentially expressed genes evoked by carbachol exclusively are closely associated with ETA and its effectors.

关 键 词：乙酰胆碱作用靶标 氨甲酰胆碱 毛果芸香碱 M受体 表达谱芯片 

分 类 号：R282.71[医药卫生—中药学] R322.12[医药卫生—中医学]