利用基因微陣列圖譜與動物之離體及活體模式評估中藥ZC008抗肝臟纖維化之功效

徐士蘭
臺中榮民總醫院
肝纖維化導致肝硬化是慢性肝病致死的重要原因。在台灣由於慢性肝炎及肝纖維化發生率高，而肝纖維化之發生又缺乏早期診斷之標記分子，且治療肝炎及肝纖維化之藥物功效不彰，導致肝硬化之病例有逐年增加之趨勢。因此尋找有效之藥物以改善肝纖維化病人的病情，及定義出診斷上可依據之分子標記便顯得格外的重要。中草藥在中國已有數千年使用之歷史，且近年來也逐漸受到西方國家的重視當作是另類療法，廣泛運用於治療許多不同的疾病，例如發炎疾病及慢性肝病（包括肝炎及肝纖維化）。本實驗室在找尋具有抗纖維化中草藥之研究中，發現其中有一中草藥（編號為ZC008，此藥物目前已申請專利中，暫時不方便公開名稱）具有顯著之抗纖維化及抑制肝發炎之現象。初步的實驗結果顯示，ZC008能有效抑制大白鼠經由二甲基亞硝胺(或四氯化碳)處理所誘發之肝纖維化及發炎反應。此份計畫中將運用各種分析方法，包括生化分析、病理分析、蛋白質電泳技術、定量RTPCR反應、RNA interference、基因轉殖、基因微陣列等技術，分析ZC008的生物功能。綜合上述的分析結果步剖析：（A）ZC008在體外培養之肝星狀細胞、肝Kupffer細胞及誘發肝纖維化之大鼠中的防治肝炎、肝纖維化之分子作用機轉；（B）利用基因微陣列的資訊，探討ZC008在肝纖維化及治癒過程中的細胞分子機轉。整體而言，此計畫的長遠目標為釐清ZC008在肝纖維化過程中的分子機轉。期望能因本計畫一系列科學化之研究驗證，將ZC008推廣為國際醫學界可接受之有效治療肝纖維化之藥物。
關鍵字：肝纖維化；基因微陣列；ZC008；肝星狀細胞；二甲基亞硝胺

Microarray profiling delineates molecular portrait of the anti-fibrosis effects of a Chinese herbal medicine, ZC008, by using in vivo and in vitro models

Shih-Lan Hsu
Taichung Veterans General Hospital, Department of Education
Progression of hepatic fibrosis is a common and potentially lethal problem in chronic liver disease in Taiwan, affecting more than 4% of the population. Incidence of cirrhosis is growing as a result of the widespread occurrence of chronic hepatitis, as well as the evident lack of an established therapy for hepatic fibrosis. The quest for the identification of an effective drug treatment to improve the outcome of patients with liver fibrosis and to develop molecular markers for liver fibrosis diagnosis is an important task. Herbal medicines have been used in Chinese population for thousands of years and there has been a growing trend in Western countries to use as alternative medicine to treat a wide range of diseases, such as inflammatory diseases and chronic liver diseases (including hepatitis and fibrosis). In the course of search for key therapeutic agents for hepatoprotective effect, a traditional Chinese medicine (ZC008, the identity of this medicine will not be released at this moment for its pending patent application in anti-fibrotic and anti-inflammation effects) begins to emerge as the winner. The results show that treatment of ZC008 can significantly prevent DMN-induced (or CCl4-induced) hepatic fibrosis and inflammation. Here, we will apply a broad spectrum of experimental approaches, ranging from traditional biochemistry, microarray, and RNA interference, in our proposal.
關鍵字：liver fibrosis；Microarray；ZC008；hepatic stellate cell；dimethylnitrosamine(DMN)