利用非侵入式多光子顯微術研究乙醯胺酚對肝臟的破壞

Utilizing Intravital Multiphoton Microscopy to Investigate Acetaminophen-Induced Liver Injury

王聖舜(Sheng-Shun Wang)

指導教授 ： 董成淵

共同指導教授 ： 李宣書(Hsuan-Shu Lee)

國立臺灣大學/理學院/物理研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.02049

摘要

乙醯胺酚為世界上通用的止痛藥與退熱劑。在美國，過量使用普拿疼是藥物造成肝破壞的主因。利用非侵入式多光子顯微術和藉由一級速度模型解析6-CFDA在肝臟細胞的強度變化，讓我們看到肝臟真正的代謝功能。我們觀察過量使用普拿疼24、48、72、96小時後肝臟細代謝的情形。另外，我們利用SYTOX Blue去準確標定死亡的肝細胞，並且比較正常與死亡肝細胞在代謝上的差異。藉由這些技術，我們可以更進一步的研究肝臟的各種疾病與機制。

關鍵字

乙醯胺酚 ； 非侵入式多光子顯微術 ； 肝膽功能

並列摘要

Acetaminophen (APAP) is a widely used as an analgesic and antipyretic agent. However, the overdose APAP ingestion is also the leading cause of drug-induced liver failure in the United States. Since the metabolic function of liver can be observed by intravital multiphoton microscopy using the intensity variation of 6-carboxyfluorescein diacetate, we used this approach to study the response of liver metabolic function from overdose of APAP after 24, 48, 72, and 96 hr administration. In addition, we used a first-order kinetic model to quantify the extent of liver regeneration. Furthermore, we used SYTOX Blue nucleic acid stain to indicate the dead hepatocytes and found that the uptake and export ability are very different between healthy and dead hepatocytes. Our methodology allows the relationship between liver diseases and metabolic mechanisms to be studied in the future.

並列關鍵字

Acetaminophen ； intravital multiphoton microscopy ； hepatobiiary function

參考文獻

1. Lee WM. Medical progress: Drug-induced hepatotoxicity. New England Journal of Medicine 2003;349:474-485.

2. Lee WM. Acetaminophen and the US Acute Liver Failure Study Group: Lowering the risks of hepatic failure. Hepatology 2004;40:6-9.

3. Palmes D, Spiegel HU. Animal models of liver regeneration. Biomaterials 2004;25:1601-1611.

4. Abella ID. Optical Double-Photon Absorption in Cesium Vapor. Physical Review Letters 1962;9:453-&.

5. Denk W, Strickler JH, Webb WW. 2-Photon Laser Scanning Fluorescence Microscopy. Science 1990;248:73-76.