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系統識別號 U0026-0608202016234400
論文名稱(中文) 羅望子木葡聚醣對由脂多醣及半乳糖胺誘發小鼠猛爆性肝炎之影響
論文名稱(英文) Effect of Tamarind Xyloglucan on Lipopolysaccharide/D-Galactosamine-Induced Fulminant Hepatitis in Mice
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 108
學期 2
出版年 109
研究生(中文) 林真襄
研究生(英文) Zhen-Xiang Lin
學號 S76061088
學位類別 碩士
語文別 中文
論文頁數 51頁
口試委員 指導教授-劉明毅
口試委員-張志欽
口試委員-吳致杰
口試委員-許德榮
中文關鍵字 猛爆性肝炎  羅望子木葡聚醣  脂多醣  半乳糖胺 
英文關鍵字 Fulminant hepatitis  Tamarind xyloglucan  lipopolysaccharide  D-galactosamine 
學科別分類
中文摘要 猛爆性肝炎是一種會危及生命的臨床綜合症,其發病時間無法預測且病程發展快速,使患者的死亡率高達80%。許多研究表明猛爆性肝炎的致病機制與病程發展,發炎反應與氧化壓力參與其中。羅望子(Tamarindus indica L.)在許多熱帶地區國家被用來作為傳統藥草,從羅望子種子中提取的羅望子木葡聚醣具有良好的抗氧化以及抗發炎作用,並且益於肝臟再生作用,但尚未有研究探討其對於猛爆性肝炎的效用,因此本研究旨在利用脂多醣(LPS)與半乳糖胺(GalN)的動物實驗誘導模式來誘發小鼠產生類似臨床的猛爆性肝炎,藉以探討羅望子木葡聚醣對於猛爆性肝炎之影響。實驗設計為將C57BL/6J雄性小鼠隨機分成五組,每組6隻。在實驗開始前三天,正常組和LPS/GalN組以餵管每天給予生理食鹽水1 ml/kg,LT1、LT3與LT10組每天給予其對應劑量1、3或10 mg/kg的羅望子木葡聚醣。於實驗開始時以腹腔注射LPS/GalN (20μg/200mg/kg)於LPS/GalN組、LT1、LT3及LT10組來誘發猛爆性肝炎,並於注射後六小時犧牲,取所有小鼠肝臟和血液進行後續分析。結果顯示,羅望子木葡聚醣可以降低肝臟損傷生化指標AST、ALT及肝臟發炎指標ALP,在肝臟切片中觀察到其減少發炎細胞浸潤與肝細胞壞死、變性情形,並且減少肝臟組織中腫瘤壞死因子-α、介白質-6、介白質-1β和介白質-10的表現量,降低脂質過氧化反應與血清中尿酸含量,增加肝臟中抗氧化物質穀胱甘肽及超氧化物歧化酶,且抑制NF-κB訊號路徑相關蛋白NF-κB、磷酸化IKK-α與磷酸化IκB-α蛋白表現量,以及降低TLR4蛋白表現量。綜合上述結果,羅望子木葡聚醣能減緩由脂多醣與半乳糖胺誘發的猛爆性肝炎,此作用可能是經由抑制TLR4/NF-κB訊號路徑的活化並降低發炎反應與氧化壓力。
英文摘要 The symptoms of fulminant hepatitis developed and become severe very quickly in days or weeks after the appearance of the first sign of liver disease. In clinical studies, the mortality is up to 80% in patients with fulminant hepatitis. Hepatic inflammation and oxidative stress have been suggested to be involved in the pathogenesis and development of fulminant hepatitis. Lipopolysaccharide (LPS)/ D-galactosamine (GalN)-induced liver injury is a well-known experimental model that closely resembles clinical fulminant hepatitis. Tamarind xyloglucan (TXG), a natural polysaccharide extracted from tamarind seeds, has excellent anti-oxidative and anti-inflammatory effects. TXG would attenuate the disease severity of fulminant hepatitis; however, the effect of TXG on fulminant hepatitis has never been investigated. The aim of this study was to investigate the effect of TXG on LPS/ GalN-induced fulminant hepatitis in mice. Male C57BL/6 mice were randomly assigned into five groups (n=6 per group): Normal group and LPS/GalN group mice were only given saline orally (1 ml/kg) for 3 days prior to LPS/GalN injection; Groups LT1, LT3, and LT10 mice were given tamarind xyloglucan (1, 3 and 10 mg/kg, orally) for 3 days prior to LPS/GalN injection. Groups LPS/GalN, LT1, LT3, and LT10 were given one injection of LPS/GalN (20 μg/200 mg/kg, i.p.). Liver and blood samples were collected 6 h after LPS/GalN injection. LPS/GalN increased serum AST, ALT, inflammatory cytokines, oxidative stress, neutrophil aggregation and hepatic histological changes. The levels of serum AST, ALT, inflammatory cytokines, oxidative stress, neutrophil aggregation and hepatic histological changes were attenuated in LT groups compared with LPS/GalN group. In conclusion, TXG may attenuate LPS/GalN-induced-fulminant hepatitis by reducing inflammation and oxidative stress via inhibition of the TLR4/NF-κB signal pathway in mice.
論文目次 摘要 I
Abstract II
誌謝 VI
圖目錄 X
壹、 研究背景 1
1.1 肝臟功能與疾病 1
1.2 猛爆性肝炎(Fulminant hepatitis) 1
1.3 猛爆性肝炎的臨床現況 2
1.4 猛爆性肝炎的病理研究 3
1.4.1 發炎反應(Inflammation) 4
1.4.2 氧化壓力(Oxidative stress) 4
1.5 脂多醣(lipopolysaccharide, LPS)與半乳糖胺(D-galactosamine, GalN)的猛爆性肝炎之動物實驗模式 5
1.6 羅望子木葡聚醣(Tamarind xyloglucan) 6
貳、 研究目的 8
參、 材料與方法 9
3.1 實驗材料 9
3.1.1 實驗動物 9
3.1.2 實驗材料 9
3.2 實驗方法 14
3.2.1 實驗動物分組與處理 14
3.3 實驗分析 15
3.3.1 血清樣本採集 15
3.3.2 血液生化分析測定 15
3.3.3 病理組織切片 15
3.3.4 測定肝臟組織內發炎細胞因子含量分析 16
3.3.5 測定骨髓過氧化酶含量分析 16
3.3.6 測定肝臟脂質過氧化(Lipid peroxidation)程度 16
3.3.7 測定穀胱甘肽(Glutathione, GSH)含量分析 17
3.3.8 測定超氧化物歧化酶(Superoxide dismutase, SOD)活性分析 17
3.3.9 測定肝臟一氧化氮(NO)含量分析 17
3.3.10 西方墨點法 18
3.4 統計分析 18
肆、 研究結果 19
伍、 研究討論 24
陸、 結論 29
柒、 參考文獻 30
捌、 圖表 37

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