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題 名 | 以基因體研究平臺為基礎進行防治肝病相關中藥之研究(2-2)=Research and Development of Chinese Medicinal Herbs for Anti-Liver Diseases by the Genomic- Based Platform (2-2) |
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作 者 | 侯庭鏞; | 書刊名 | 中醫藥年報 |
卷 期 | 29:8 2011.09[民100.09] |
頁 次 | 頁233-264 |
專 輯 | 中醫藥基因體相關研究 |
分類號 | 414.33 |
關鍵詞 | 肝病; 中草藥; DNA微陣列; Liver diseases; Chinese medicinal herbs; DNA microarray; |
語 文 | 中文(Chinese) |
中文摘要 | 研究目的: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、三黃瀉心湯等,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,不過許多中草藥的作用機制並不清楚,而且中草藥於新藥開發的應用仍有很大的發展空間。 研究方法:本計畫主要利用DNA 微陣列為工具,分析中草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,並將資料庫應用於中草藥之作用機轉、傳統中醫藥之現代藥性、新藥的開發及臨床前藥物安全性之分析。 結果與結論:在中藥生物活性基因圖譜資料庫方面,我們已建立一套標準操作流程來執行,標準操作流程包括細胞加藥或是動物給予藥物的流程管控、萃取RNA 時的細胞狀況管控、萃取RNA 的質和量的管控、DNA 微陣列實驗以及數據分析過程的品質管控等。在中藥生物活性基因圖譜資料庫的建立及分析方面,我們已經進行健保常用方藥及肝病常用方藥之轉錄體學分析。將這些方藥給予小鼠,萃取肝臟和腎臟的RNA 進行DNA 微陣列分析,再藉由Pathway 分析後,發現除了代謝相關的pathways 以外,antigen processing and presentation pathways 及IGF signaling pathways 也受到這些方藥的調控與影響。而在疾病相關性的分析方面,發現與方藥相關的前30 名MeSH disease terms 主要是與diabetes-associated、cardiovascular 以及hepatic 相關的疾病。另外,連結方藥與Connectivity Map 的基因表現圖譜,發現方藥與抗癌、抗發炎以及抗氧化方面的西藥或化合物有較高的相似性。最後,我們分析毒理相關基因的表現,我們藉助223 個化學藥物所構建的 toxicology-related cDNA 微陣列的資料庫,比對方藥處理至動物腎臟毒理代謝相關基因的表現情形,發現兩者趨勢不同且圖譜相距甚遠。因此,我們認為中醫方藥在toxicology-related genes 的基因圖譜表現上與化學藥物是有所區別的,也表示,中醫方藥處理至實驗動物後,其藥物在腎臟毒理方面是無顯著急性顧慮的。其他常用肝病方藥之生物活性基因圖譜正在持續擴充及分析中,未來預計開發新的生物資訊程式用以進行中藥方劑與疾病和西藥相關性的分析,進一步則期望能將中藥生物活性基因圖譜資料庫所含的大量資訊和既有的傳統中醫知識做整合與對應。 |
英文摘要 | Aim: Although several herbal formulae and herbal components have been used in patients with liver diseases, their applications in new drug development remain to be discovered. Method: We apply microarray technology to analyze and explain the modern biological activities of medicinal herbs. The gene expression databases established in this project can further provide the basis for the herb-activity relationship, modern definition of Traditional Chinese Medicine (TCM), new drug development, and preclinical drug safety analysis. Results and Discussion: The gene expression databases were established according to the standard operation protocols, including quality controls of drug treatment, cells, RNA extraction, microarray, etc. Microarray data have been used to establish and analyze the gene expression profiles of herbal formulae that are regularly used in the treatment of liver diseases in TCM. Mice were orally administered with herbal extracts, and the gene expression signatures from livers and kidneys were analyzed by DNA microarray. By Pathway analysis, we found that herbal formulae affected metabolism-related pathways as well as antigen processing and presentation pathways and IGF signaling pathways. Connectivity Map analysis showed that top 30 MeSH disease terms related to the gene expression signatures of herbal formulae were diabetes-associated diseases, cardiovascular diseases, and hepatic diseases. Moreover, the gene expression profiles of herbal formulae were similar to the ones of drugs or compounds with anti-cancer, anti-inflammatory, and anti-oxidative abilities. Finally, clustering analysis of gene expression signatures from herbal formulae and toxicology-related database from 223 chemicals showed that herbal formulae and 223 chemicals belonged to two different clusters. These findings indicated that administration of herbal formulae did not induce acute nephro-toxicological effects in mice. In conclusion, the microarray-based gene expression database of herbs can provide a translation platform for TCM and scientific knowledge. |
本系統中英文摘要資訊取自各篇刊載內容。