肝臟貼片應用於四氯化碳毒化後之肝臟回復的研究

Abstract

肝臟在人體中扮演著不可或缺的角色，其具有蛋白質合成、尿素代謝以及解毒等重要機能。隨著人們藥物濫用，飲食習慣改變等，肝纖維化乃至於肝硬化日益普及。過往的研究提出自體性物質 (例如白細胞介素-10、肝細胞生長因子等) 的補充可以逆轉肝纖維化，但效率不彰，因此如何將「自體性物質」有效地作用於肝纖維化的患部去逆轉肝纖維化是科學家亟需解決的問題。為了解決這個問題，本研究將開發一新穎的生物材料來製作肝臟貼片使被毒化後的肝臟之機能能夠回復。 本研究第一部分主要致力於肝臟貼片的製作，利用脫細胞化肝臟間質 (Decellularized liver matrix; DLM) 為基底，並於其上方修飾肝細胞生長因子 (Hepatocyte growth factor; HGF)/肝素 (Heparin) 錯合物，除了檢測該材料的性質之外，亦實際將其應用於體外藥物毒化 (CHCl3, CCl4) 後的肝細胞之回復。第二部分則首先致力於建立大鼠體內四氯化碳 (Tetracholoride; CCl4) 誘導之慢性肝纖維化模型，我們接著以第一部分所開發的肝臟貼片對於上述慢性肝纖維化之回復的影響進行檢測。本研究期許此肝臟貼片未來能實際應用於臨床治療，並為肝病治療給予新的方法與展望。

The liver plays an indispensable role in the human body with important functions such as protein synthesis, urea metabolism, and detoxification. However, due to drug abuse and the change of diet habit, liver fibrosis or even liver cirrhosis exists much more commonly. Previous studies show several treatments to reverse liver fibrosis by adding autologous substrates (ex. interleukin-10, hepatocyte growth factor), but with low efficiency. Thus, what the scientists heading for is the elevation of the efficiency. In order to overcome the obstacle, this study aims to develop a new biomaterial (with a few autologous substrates) to manufacture liver patch for regeneration of chemicals induced liver injury. This research is planned to be carried out within two years. In the first year, we focus on the manufacture of liver patch (hepatocyte growth factor HGF/heparin complex coating on decellularized liver matrix DLM) and the measurement of the characteristics of the material. Furthermore, we utilize liver patch to the regeneration of chemicals induced liver injury in vitro. In the second year, we commit to in vivo study inclusive of CCl4 induced liver fibrosis, then attach liver patch to fibrotic liver for reversing the fibrotic process. This study is believed to be applied in clinical applications and give us new methods and prospects for the treatment of liver disease in the near future.