基因芯片研究蟾酥急性毒性及配伍减毒机制  

Acute Toxicity of Venenum Bufonis and Compatibility of Heart Musk Protecting Pills by Microarray Expression Analysis

作　　者：杨爱文[1,2] 范雪梅[2] 李雪 梁琼麟[2] 王义明[2] 罗国安[1,2] 

机构地区：[1]华东理工大学药学院,上海200237 [2]清华大学中药现代化研究中心 [3]医学院,北京100084

出　　处：《高等学校化学学报》2011年第5期1058-1064,共7页Chemical Journal of Chinese Universities

基　　金：国家“新药创制”科技重大专项(批准号:2008ZX09202,2009ZX09311-001);国家“十一五”科技支撑计划项目(批准号:2006BAI08B04-01)资助

摘　　要：利用基因芯片技术研究了蟾酥对大鼠心脏的急性毒性及其组方成麝香保心丸后的配伍减毒机制.通过表达谱芯片检测了药物作用后的基因表达差异,对差异表达基因进行了生物信息学研究并结合实时荧光定量PCR分析.结果表明,低剂量蟾酥可以通过干扰离子稳态和肌动蛋白构建来影响心脏的收缩,同时还会导致心脏细胞的抗凋亡和脂类代谢等应激反应;高剂量蟾酥除进一步干扰离子稳态和肌动蛋白构建外,还会引发铁离子蓄积,最终可能导致细胞凋亡;且蟾酥对心脏的影响具有剂量依赖性.当蟾酥组方成麝香保心丸后,上述影响均不明显,主要影响血压调节和心肌修复等作用,体现了中药配伍的减毒作用.The differentially expressed genes involved in acute toxicity and compatibility of Heart Musk Protecting Pills（HMP） via cDNA microarray were investigated in this paper. Then the GO and KEGG pathway enrichment analysis were performed as well as the functional analysis and RT-PCR validation of two important genes. The results indicated that the ion homeostasis and actin organization were affected in the low dosage group for Venenum Bufonis. Meanwhile, regulation of anti-apoptosis and fatty acid metabolism could be induced within 2 h ; the myocardial contraction was finally could also be disturbed more quickly in the high dosage disturbed. The ion homeostasis and actin organization group. In addition, the iron accumulation could lead to oxidation reduction and cardiomyocyte apoptosis. For HMP, there were some clinical functions, such as blood pressure regulation and myocardial structure organization. However, the related acute toxicity of Venenum Bufonis was not shown. This paper could provide a novel research strategy in the compatibility study of traditional Chinese medicine （TCM）.

关 键 词：基因芯片 实时荧光定量PCR 蟾酥 麝香保心丸 急性毒性 中药配伍 

分 类 号：O657[理学—分析化学]