以基因體研究平臺為基礎進行防治肝病相關中藥之研究
侯庭鏞
中國醫藥大學
肝病是國人健康的大敵，也是最大的本土病。根據衛生署94年度國人死因統計，肝癌（hepatocellular carcinoma）為癌症死因第二名，而慢性肝炎（chronic hepatitis）及肝硬化（cirrhosis）也排名十大死因的第六名。中醫利用方劑及單味藥治療肝病已有長久的經驗，例如小柴胡湯、龍膽瀉肝湯等，都是常見的治肝病方劑。雖然這些中草藥療法已有長久的臨床使用經驗，而且獲得不錯的效果，不過許多中草藥的作用機制並不清楚。因此，本計畫擬以肝病相關中醫方劑、中藥、中藥標準品及其它現代常用治療肝病之西藥為主要對象，以DNA微陣列為分析工具，利用藥物處理適當細胞，藉由萃取RNA並經cDNA合成、螢光標定、雜合反應後，分析中藥對細胞基因的生物活性反應，以建立一套完整的中藥生物活性基因圖譜資料庫。進一步以此資料庫為起點，藉由分析臨床上治療肝病常用之西藥的基因表現圖譜，利用相同生物活性基因圖譜可能具有相同藥性的概念，評估中藥是否具有相似之基因表現圖譜，以成立中藥基因體新藥開發評估平台。此外，藉由某些特定基因與毒性及特定生物功能（例如腫瘤生成、腫瘤轉移）具相關性的概念，評估中藥潛在的藥性及毒性。本計畫所建立的生物活性基因圖譜資料庫，除了提供抗肝病中草藥的藥效/成份相關性、品管的新標準及一個新的中醫藥基因體研究技術平台外，也可與西藥的基因反應圖譜比對分析，分析中藥現代藥性及毒理反應，以導引中藥新藥及中藥保健食品的開發。
關鍵字：肝病；中草藥；DNA微陣列
Research and Development of Chinese Medicinal Herbs for Anti-Liver Diseases by the Genomic-Based Platform
Ho, Tin-Yun
China Medical University
Liver diseases remain leading global health problems. For examples, hepatocellular carcinoma is the second most common cause of cancer in Taiwan, and chronic hepatitis and cirrhosis are the sixth common cause of death in Taiwan. Chinese herbal medicine has been used for the treatment of liver diseases for years. Although several herbal formulae and herbal components have been used in patients with liver diseases, their molecular mechanisms remain to be discovered. Therefore, we will establish a large-scale DNA microarray-based gene expression database of Chinese medical herbs with anti-liver disease potential. The gene expression databases established in this project could further provide the basis for the herb-activity relationship, modern definition of Traditional Chinese Medicine, new drug development, and preclinical drug safety analysis. Based on the similarity between gene expression profile and therapeutic activity, we can classify the medicinal herbs and speed up the new drug development. Based on the relationship between specific genes and pathogenesis, we can predict the therapeutic potential of herbs. Based on the expression levels of cytotoxicity-associated genes, we can evaluate the herb safety. In conclusion, this project will integrate a large-scale database of gene expression profiles of medicinal herbs and molecular pharmacology.
關鍵字：Liver diseases；Chinese medicinal herbs；DNA microarray
