基因芯片研究蟾酥急性毒性及配伍减毒机制

利用基因芯片技术研究蟾酥对大鼠心脏的急性毒性和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药物作用后的基因表达差异，对差异表达基因进行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；蟾酥组方成麝香保心丸后，上述的影响均不明显，主要影响到血压调节和心肌修复等作用，体现了中药配伍的减毒作用。

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

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 carried as well as the functional analysis and real time RT-PCR validation of two important genes. 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 two hours; the myocardial contraction was finally disturbed. The ion homeostasis and actin organization could also be disturbed more quickly in the high dosage 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).