| Abstract: | 人類使用不同形式的nonsteroid antiinflammatory drugs (NSAIDs)已超過3500年以上。至今仍是人們最愛使用、最常使用的藥物。估計每年消耗約40000噸的aspirin，若以每錠300 mg的標準劑量換算，大約為12億顆aspirin藥錠。然而，除了其傳奇的歷史與龐大的使用量外，對於NSAIDs的作用機制事實上尚未完全了解。研究發現使用aspirin於DM患者，患者心血管病變率雖未達顯著性改變但亦有7%的降低。由於仍缺乏足夠證據，因此使用aspirin於DM患者作為心血管病變的得失仍有待商確。本計畫之目的乃在探討aspirin對脂肪生成作用相關之訊息傳導。本計畫規劃:第一年為細胞階層實驗、第二年則為動物實驗。第一年：以3T3-L1前脂肪細胞為對象，以建立各訊息傳導路進之理論基礎。第二年規畫為動物實驗，用以驗證前述之各項理論。 對於本計畫我們已進行部分先期實驗例如以血液生理濃度之aspirin (0.0001~0.1μM)處理3T3-L1前脂肪細胞(preadipocyte)，以探討其對glucose uptake、adipogenesis之作用與相關訊息傳導路徑。先期實驗中我們獲得一些初步結果以供日後實驗參考。例如aspirin誘發3T3-L1細胞生長、降低glucose uptake、抑制脂肪生成。ERK1/2抑制劑PD98059增進aspirin誘發脂肪細胞生長的作用、增進aspirin抑制glucose uptake的作用、伴隨aspirin處理脂肪生成顯著的增加。p53抑制劑pifithrin單獨或伴隨aspirin處理3T3-L1細胞對於細胞生長、glucose uptake、adipogenesis皆無顯著作用。
Humans have been using nonsteroid antiinflammatory drugs (NSAIDs) in various forms for more than 3,500 years. They are still our favorite medicines. Estimates vary, but it appears, for instance, that each year we consume around 40,000 metric tons of aspirin, equating to about 120 billion aspirin tablets (300 mg is a standard size). However, despite this long history and large volume of use, we still have an incomplete understanding of how the NSAIDs achieve their actions. There is a two- to fourfold increase in risk of death in patients with DM compared with those without. A number of aggressive interventions are used in the treatment and prevention of cardiovascular disease in DM. A part of such treatment is the use of antiplatelet medication, namely aspirin (acetylsalicylic acid). In primary prevention studies, a meta-analysis by the Anti-Platelet Trialists’ Collaboration reported a non-significant 7% reduction in cardiovascular events in those with DM. Thus, the benefit of using aspirin in DM for primary prevention of cardiovascular events remains unclear. The purpose of this project is studying the signaling of NSAIDs in adipogenesis. At the first year, it is cell-level experiment. We use 3T3-L1 preadipocyte to study the signaling of adipogenesis. In preliminary studies, the result showed (1). Aspirin induced 3T3-L1 cell growth, decreased glucose uptake and inhibited adipogenesis. (2).ERK1/2 inhibitor (PD98059) increased 3T3-L1 cell growth with aspirin, increased the inhibition of glucose uptake of aspirin, induced adipogenesis with aspirin. (3). Pifithrin (p53 inhibitor) with or without aspirin, there is no significant difference in 3T3-L1 preadipocyte growth, glucose uptake and adipogenesis. At the second year, we use animal model to prove the result showed at first year. |
