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研究生： 郭加敏
Kuok, Ka-Man
論文名稱： 以動物實驗建立模式---棕色脂肪活化對肝臟部分切除術後產生的脂肪肝之影響
Brown fat activation-altered liver Steatosis in an animal model of partial hepatectomy
指導教授： 沈延盛
Shan, Yan-Shen
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床醫學研究所
Institute of Clinical Medicine
論文出版年： 2024
畢業學年度： 112
語文別： 英文
論文頁數： 35
中文關鍵詞： 非酒精性脂肪肝病 、肝切除 、肝臟再生 、寒冷環境暴露 、棕色脂肪
外文關鍵詞： Nonalcoholic Fatty Liver Disease (NAFLD), Hepatectomy, Liver regeneration, Cold exposure, Brown fat
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    • 在臨床上活體肝臟移植中，器官捐贈者遭到大面積的肝臟切除術後，因手術後將面臨非酒精性脂肪肝病（NAFLD）和相關的代謝性疾病的影響，有可能進展為脂肪肝炎，甚至肝癌等肝臟疾病。本研究中利用暴露於寒冷環境的治療方法增進棕色脂肪的增生，並且達到改善這種不可逆的肝臟病變的進程。在我們的研究中，首先建立一個肝臟切除後的動物模型，來確認肝臟再生的情形。利用C57BL/6小鼠，在正常飲食餵養，室溫飼養至8週大，並接受肝臟切除手術以誘導肝臟脂肪病變的發生。再來就是想改善這種不可逆的脂肪肝病變，使用另一種實驗方法是將小鼠每天暴露在4 ℃ 環境下12小時促進活化棕色脂肪組織的增生，並增進改善肝臟再生過程中肝臟脂肪變性的變化。我們發現到暴露於寒冷的環境中對肝臟再生有保護作用。首先，它可以對抗肝切除後引起的肝臟脂肪變性、肝臟指數昇高和代謝異常。其次，暴露於冷環境中可誘發棕色脂肪的增生以及棕色脂肪UCP1的表現增加。同時，寒冷暴露會調降肝臟缺氧和肝臟脂肪代謝等因素，例如HIF1和PPARγ。第三，我們的研究結果顯示冷暴露不會阻礙肝臟再生。因此，我們的研究證實利用冷環境的暴露治療對不可逆的肝功能障礙、相關的代謝性疾病和 NAFLD得以改善的希望。

    In living liver transplantation, donors with liver damage will have a large area of liver parenchyma removed, and they will face the impact of postoperative nonalcoholic fatty liver disease (NAFLD) and metabolic diseases after surgery. It is hoped that the treatment method of cold environment exposure can change this irreversible liver disease process. In our experiments, an animal model was first established. C57BL/6 mice were fed a normal diet, raised at room temperature until they were 8 weeks old, and underwent significant liver resection surgery to induce liver steatosis. The other is exposure to 4 ℃ for 12 hours a day. Endogenous brown adipose tissue is activated by cold exposure. Improve the changes in hepatic steatosis during liver regeneration. We found that cold exposure has a protective effect on the liver. First, it counteracts liver steatosis, liver index, and metabolic abnormalities caused by liver resection. Secondly, cold exposure reverses white fat's proliferation and brown fat's direction, and the expression of UCP1 in brown fat is up-regulated. At the same time, cold exposure downregulates factors such as liver hypoxia and liver fat metabolism, such as HIF1 and PPARγ. Third, our results indicate that cold exposure does not impede liver regeneration. Therefore, our study reveals the hope of using cold exposure to treat irreversible liver dysfunction, metabolic diseases, and NAFLD.

    中文摘要 1 Abstract 2 Content 3 Abbreviations 5 INTRODUCTION 6 Rationales and Specific Aims 9 MATERIALS AND METHODS 10 Animal model 10 Partial hepatectomy 10 Regenerated liver weight 11 Cold exposure treatment 12 Metabolic profile 12 Histological and immunohistochemically examinations 13 Statistical analysis 14 RESULTS 15 We have successfully established a fatty liver steatosis mouse model through liver resection surgery 15 Cold exposure can improve hepatic steatosis after hepatectomy by changing the hypoxic environment. 17 Cold exposure does not affect liver regeneration after hepatectomy and can also improve changes in hepatic steatosis. 19 Conclusions 21 Discussion 21 Reference 24 Figures 26 Figure 1. The flow chart of raising mice, performing liver resection, and collecting body specimens after surgery. 26 Figure 2. H&E histology and cell proliferation of liver regeneration under different degrees of liver resection. The value of Ki67 positive was recorded for POD and averages (mean+ SEM). 27 Figure 3. The cold exposure experiment involves exposing mice to a cold environment and then undergoing liver resection to observe liver regeneration. 28 Figure 4. Changes in interscapular brown fat in mice after cold exposure 29 Figure 5. This chart shows that under different circumstances, H&E staining can show the accumulation of fat in liver cells. 30 Figure 6. Effects of different degrees of liver resection on postoperative biochemical indexes 31 Figure 7. Comparison of liver regeneration weight in different groups after hepatectomy. 32 Figure 8. Effects of minor liver resection, major liver resection, and liver resection after cold exposure on different biochemical indexes 33

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