臺灣博碩士論文加值系統

非酒精性脂肪肝疾病 (nonalcoholic fatty liver disease, NAFLD) 是世界上常見的肝臟疾病之一，其致病原因可歸納為脂肪酸合成增加或脂肪酸分解減低。高比例之非酒精性脂肪肝將發展為肝纖維化、肝硬化甚至肝癌。鹿茸被作為傳統中藥材及健康食品已長達兩千年，本研究乃在探討台灣水鹿鹿茸萃取液是否以及如何降低小鼠非酒精性脂肪肝之形成。將雄性 C57BL/6JNarl 小鼠分成五組：正常組、對照組及三個處理組 (每日分別給予100、200、400 mg/kg之鹿茸醋萃取液)，其中對照組和三個處理組皆藉由飼予高果糖玉米糖漿及高脂飼料誘導出非酒精性脂肪肝，而正常組則給予蒸餾水及標準飼料。結果顯示對照組之體重顯著較正常組者為高，且顯現出許多NAFLD之特徵。雖然對照組與處理組之體重、脾臟、腎臟、肝臟重量皆無顯著差異，但與對照組相比，鹿茸萃取物能顯著降低小鼠血清中 ALT、AST 值以及肝臟中 TNF-α、IL-6、TSLP、IL-33、CCL2 和三酸甘油脂的含量。另外，組織學檢查顯示中鹿茸萃取液可緩解高果糖玉米糖漿及高脂飼料所引起之脂肪肝。因此，鹿茸萃取液也許可以預防高脂高果糖飲食所引起之脂肪肝疾病。

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. The NAFLD is attributed to the increase in fatty acid synthesis or decrease in fatty acid β-oxidation. Nonalcoholic fatty liver disease is associated with increased lipid contents in liver and serum. Recent studies have suggested that some NAFLD patients may develop into liver fibrosis, cirrhosis, or even hepatocellular carcinoma. Velvet antler has been used in traditional Chinese medicines and health foods about 2000 years. In the present study, we investigated whether and how the velvet antler extract of Formosan sambar deer (Cervus unicolor swinhoei) prevents the onset of NAFLD in murine model. Male C57BL/6JNarl mice were randomly allotted into five groups: naïve group, control group, and three treatment groups which were administered with 100, 200, and 400 mg/kg respectively, velvet antler vinegar extracts (VAE) daily, by gavage for 16 weeks. The control and the treatment groups were offered high-fructose corn syrup and high-fat diet (HFHF) ad libitum to induce NAFLD, while the naïve group was offered distilled water and normal diet ad libitum. Results showed that the control group had a higher body weight than the naïve group, and exhibited many characteristics of NAFLD. There were no significant differences between control group and treatment groups in body weight and weights of spleen, kidney, and liver. Velvet antler extracts significantly lowered serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) activities as well as hepatic tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), CCL2/monocyte chemotactic protein-1 and triglyceride contents, compared with control group. On the basis of histology, VAE alleviated the fatty liver led by HFHF diet. It is concluded that velvet antler extracts may be an idea alternative medicine for preventing HFHF-induced NAFLD.

目錄
壹、 摘要 1
貳、 前言 2
參、 文獻回顧 4
一、肝臟之功能及代謝性傷害 4
(一) 肝臟之碳水化合物代謝 4
(二) 肝臟之脂肪代謝 6
(三) 肝臟對蛋白質及胺基酸之代謝 12
(四) 果糖對肝臟之損害 14
(五) 高脂肪飲食對肝臟之損害 17
(六) 非酒精性脂肪肝疾病之成因 18
(七) 發炎與肝臟病變的關係 19
二、鹿茸之安全與應用 23
(一) 鹿茸之解剖與生理 23
(二) 鹿茸之組成分 26
(三) 鹿茸之藥理作用 29
(四) 鹿茸之毒性與副作用 33
肆、 研究目的與動機 34
伍、 材料與方法 35
一、藥品材料 35
二、實驗方法 37
(一) 鹿茸萃取物製備流程 37
(二) 鹿茸萃取物胺基酸含量之HPLC (high performance liquid chromatography) 分析 37
(三) 動物飼養與試驗分組 40
(四) 脂肪肝造型模式 41
(五) 血液採集與血清分離 41
(六) 口服葡萄糖耐受性試驗 41
(七) 血清胰島素含量測定 41
(八) 血清中AST (aspartate aminotransferase) 活性測定 42
(九) 血清中ALT (alanine aminotransferase) 活性測定 42
(十) 血清中三酸甘油酯濃度測定 42
(十一) 血清中總膽固醇濃度測定 42
(十二) HOMA-IR計算 43
(十三) 肝臟組織學檢查 43
(十四) 肝臟三酸甘油酯及總膽固醇濃度分析 44
(十五) 肝臟細胞激素濃度測定 44
三、統計分析 45
陸、 結果 46
一、鹿茸胺基酸成分分析 46
二、鹿茸對非酒精性脂肪肝疾病之保護作用 47
(一) 小鼠之體重、總增重、臟器與脂肪重量 47
(二) 口服葡萄糖耐受性試驗 50
(三) 胰島素敏感性 52
(四) 肝臟內三酸甘油酯及總膽固醇濃度 53
(五) 血清中三酸甘油酯及總膽固醇濃度 54
(六) 血清肝功能指標測定 55
(七) 肝臟外觀形態圖 56
(八) 肝臟病理組織學檢查 57
(九) 肝臟細胞激素 (TNF-α、IL-6、CCL2、IL-33、TSLP) 59
柒、 討論 60
捌、 結論 66
玖、 參考文獻 67
Abstract 92
壹拾、 小傳 93
壹拾壹、 附件 94
附件一、實驗動物審查同意書 94
附件二、生醫年會摘要 95

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