目的寻找生川乌的毒性基因，探讨其毒性机制。方法根据国际ICH的要求，在SPF实验条件下采用生川乌水煎液ig昆明种小鼠进行毒性实验。采用基因表达谱技术，就生川乌对小鼠5种脏器的毒性进行全基因组描绘，应用Cluster、GO和Pathway等生物信息学手段对获取的数据进行综合分析并进行定量PCR验证。结果生川乌明显影响小鼠黏着斑(Focal adhesion)通路中的黏附素(ECM)、局部黏附激酶(FAK)和GTP结合蛋白(Cdc42)等关键基因。结论生川乌可能是通过影响小鼠Focal adhesion信号通路的关键基因而引起毒性，最终导致毒性的产生。

Objective To study the toxicity and its mechanism of Radix Aconitii from genetic and molecular levels.Methods According to the requirements of ICH,the acute toxicity experiment was carried out under the condition of SPF by ig administration of the decoction of Radix Aconitii to mice.Gene expression profiling was used to describe whole-genome of five organs in mice,the related data were analyzed by using bioinformatics statistics,such as Cluster,GO,and Pathway,and the results were validated through quantitative PCR.Results The effects of Radix Aconitii on the key genes of the Focal adhesion pathway of mice,such as ECM,FAK,Cdc42,were remarkably.Conclusion The reason why Radix Aconitii produces the toxicity is probably that Radix Aconiti could cause the toxicity of Focal adhesion signal pathway through influencing the key genes.

国家自然科学基金重点项目（30230410）