蟾蜍靈對細胞發炎反應的效益評估及其作用機制和標的分子探討

吳鈺琳
國立陽明大學生理學研究所
不論在生物醫學及中國傳統醫學的領域中，疾病與疾病導致的基因改變以及藥物的作用等三面向的關連一直是很重要的研究目標。但是在實驗室的層級中如何發現適用的中草藥及如何釐清中藥作用的標的分子及相關機轉一直是很重要的工作。中藥的特色之一是常具有既能抗發炎又能增強免疫力的生物活性。而發炎反應是全身各組織均會發生的重要生理功能，然而失調的發炎反應卻也會對身體造成危害例如敗血症即是臨床上常見且非常嚴重的發炎症狀。所以瞭解中藥在免疫系統中如發炎反應的效用顯然非常重要。在傳統中藥的蟾酥，其主要作用為強心和局部麻醉，而蟾酥的主要成分之一蟾蜍靈(bufalin)則是屬於具心臟活性之類固醇，具有止痛效果。另外蟾蜍靈對於癌細胞的相關治療研究也已經十分深入，然而對蟾蜍靈在細胞發炎反應的藥效則未有任何相關報導。所以本研究計畫將伸入探索蟾蜍靈對細胞發炎反應的影響並確認其作用方式和標的基因。在本計畫中有兩個主要的目標：一、於細胞層級以細胞學，生化學及分子生物學角度探討蟾蜍靈對發炎反應之效用及機制。二、結合生物晶片分析之結果，建立蟾蜍靈之標的基因群；並利用系統生物學的工具探討蟾蜍靈與訊息傳遞路徑之間以及與蛋白質之間的聯繫網絡及交互作用關係。預期我們的研究成果同時也可能對治療或預防發炎反應相關疾病提供了更佳的選擇。
關鍵字：蟾蜍靈;發炎反應;訊息傳遞

Significance of Bufalin in Cellular Inflammatory Cascades

Yuh-Lin Wu
Department of Physiology, National Yang-Ming University
Interaction between diseases, disease-modifying genes, and herbal modulators of those gene products has been a top aim of biomedical research as well as the core of Chinese medicine. It has been a critical goal in lab to locate herbal molecules with identoified novel functions, to delineate the related mechanisms, and to identify the target molecules or genes of the pure herbal molecules. One feature of Chinese medicine is that it is able to perform an anti-inflammatory and/or to promote body immune activities. Inflammation is a normal physiological process, which occurs in a variiety of tissues; however, unharmonious inflammation may result in devastating outcomes, such as sepsis. Bufadienolides are extracts of toxic glands from toads, and used as anticancer agents mainly on leukemia cells. However, the potential contribution of bufadienolides to the inflammatory process remains mostly unclear. Thus, this project is aiming to investigate a pure component of bufadienolides, bufalin, to evaluate its effects on cellular inflammatory cascades, to pinpoint the involving molecular mechanisms, and to identify its potential target genes in a global scope. There will be two specific aims in this proposal. Aim 1: In cell culture models, we will illustrate the impacts of bufalin on cellular inflammatory cascades from cellular, biochemical and moleculr biological aspects. Aim 2: With the microarray assays, we will disclose the whole panel of the target genes of bufalin and by using systematic biology technique we will also seek to examine the intriguing connection between bufalin and any candidate signaling molecules (pathways). Our findings will expand the knowledge of if and how bufalin contributes to the inflammatory process. We will also anticipate the identification of novel target genes of bufalin to provide valued options for treating inflammation-related diseases.
關鍵字：Bufalin; Inflammation; Signal transduction