应用基因表达谱芯片研究黄药子对小鼠肝脏的毒性机制(简报)

STUDY ON THE HEPATOXICITY MECHANISMS OF HUANGYAOZI (RHIZOMA DIOSCOREAE BULBIFERAE) ON MOUSE LIVER BY cDNA MICROARRAY

黄药子为薯蓣科植物黄独（Dioscorea bulbiferaL.）的块茎，临床常用于治疗甲状腺肿、抗肿瘤、抗炎、抗病毒等。近年来临床上关于黄药子的毒副作用，尤其是对肝、肾的不良反应屡有报道。当黄药子或其代谢物在肝细胞内累积时会直接干扰肝细胞代谢，病变肝组织在形态上表现出脂肪样变、嗜酸样变性、小灶性坏死或片状坏死，且肝损伤程度与给药剂量和时间密切相关。目前，关于黄药子的肝毒成分一般认为是其所含的薯蓣皂苷、薯蓣毒皂苷、黄药子萜ABC及鞣质等，但关于黄药子肝损伤的病理过程与分子机制还不清楚。

cDNA microarray-technique was used to study the mechanisms of liver injury caused by Huangyaozi at level of gene expression based on the biological functions of those differentially expressed genes. For the mice taking Huangyaozi for 15 days,there were 83 differentially expressed genes,among them 18 genes were up-regulated and 65 genes were down-regulated, and the increase of serum ALT,AST and tissue total protein were notable. For the mice taking Huangyaozi for 30 days, there were 1658 differentially expresses genes,among them 917 genes were up-regulated and 741 genes were down-regulated. And the liver index,serum ALT and tissue total protein were all increased significantly but AST,AKP decreased significantly. There genes in the two groups,among them 9 genes were up-regulated,while the other 36 genes were down-regulated. According to the differentially expressed genes with different duration for taking Huangyaozi,the phased change about occurrence and development of liver injury was analyzed. The results indicated that the gene expression profile of mouse liver cell could be changed significantly by taking Huangyaozi ,which might be important for elucidating the mechanisms of liver injury caused by Huangyaozi.