脫細胞化肝臟間質之奈米載體的開發與其於肝臟再生之應用

Development of a decellularized liver matrix-based nanomedicine for liver regeneration

邱裕銓(Yu-Chuan Chiu)

指導教授 ： 侯詠德

國立臺灣大學/生物資源暨農學院/生物機電工程學系/碩士(2022年)

https://doi.org/10.6342/NTU202203616

摘要

肝臟是人體中相當重要的器官，在循環系統中亦主要扮演代謝物質的角色，體內的蛋白質合成、碳水化合物代謝、脂質代謝、以及排毒等都是肝臟負責的重要機能。然而慢性肝炎一直是國人十大死因之一，過往的研究提出水飛薊素可以改善慢性肝病的症狀，但效率不彰；此外，由於肝臟所肩負多種生理作用，因此肝功能障礙往往使得肝病患者在手術治療期間會增加發病和死亡的風險。因此臨床上迫切需要能夠提升肝病患者之肝再生能力的標靶藥物、並透過與手術搭配應用的輔助性療法，讓更多肝病病患得以進行手術治療並提高其成功率。為了突破這個困境，本研究將開發一新穎的奈米載體，以促進部分肝切除術後的肝臟機能之回復效率。
本研究主要分為兩個部份進行。第一部分致力於奈米載體的開發 (以 mPEG 修飾之脫細胞化肝臟間質) 及其奈米載體的性質檢測。第二部分則是將大鼠初代成熟肝細胞與奈米載體進行共培養並觀察細胞活性與肝臟機能檢測；此外，亦嘗試建立小鼠體內 2/3 部分肝切除模型、並檢測包埋單寧酸之奈米載體對於部分肝切除術後小鼠肝臟再生之影響。本研究期許未來能實際應用於臨床治療，為肝病治療給予新的方法與展望。

關鍵字

脫細胞化肝臟間質 ； 奈米粒子藥物傳遞系統 ； 單寧酸 ； 部分肝切除 ； 肝臟再生

並列摘要

The liver plays an indispensable role in the human body with important functions such as protein synthesis, urea metabolism, and detoxification. However, chronic hepatitis ranks top 10 in the most common causes of adult deaths worldwide. Silymarin has long been used as an ideal reagent for the comparison of hepato-protective bioactive components, but absorption of oral silymarin is low with poor bioavailability. On the other hand, liver dysfunction often puts liver-diseased patients at increased risk of morbidity and mortality during surgical operation, for more patients which can undergo surgical operation and improve their success rate, development a targeted drug which can improve liver regeneration in liver-diseased patients seems to be urgent.
Thus, a mPEG-modified decellularized liver matrix (mPEG-DLM) was developed for improving the hepatic functions after partial hepatectomy (PH). We firstly synthesized the mPEG-DLM and determined its characteristics, then, the cell viability and hepatic functions of mPEG-DLM were checked in vitro, furthermore, the establishment of 2/3 PH in vivo model was confirmed, and the effect of tannic acid (TA)-embedded mPEG-DLM on liver regeneration after 2/3 PH was further clarified. This study may have potential in clinical applications and can give us new prospects for the treatment of liver disease in the near future.

並列關鍵字

Decellularized Liver Matrix ； Nanoparticle Drug Delivery System ； Tannic Acid ； Partial Hepatectomy ； Liver Regeneation

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