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Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12836
標題: 不同程度之甲狀腺素在大鼠利用硫代乙醯胺誘導之肝纖維化的影響
The effect of different thyroxin level on rats with liver fibrosis induced by thioacetamide
作者: 李銘偉
Lee, Ming-Wei
關鍵字: Liver fibrosis;肝纖維化;Thioacetamide;Thyroxin;Matrix metalloproteinase;乙醯硫代胺;甲狀腺素;基質金屬蛋白酵素
出版社: 獸醫學系暨研究所
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摘要: 
肝纖維化是由於不同病因造成連續性的肝臟傷害所導致。在肝纖維化的形成中，活化的肝臟星狀細胞轉變成肌纖維母細胞，並且在過成中增加膠原的合成與分解的減少。許多研究指出甲狀腺功能低下症可以減少大鼠肝臟的損傷及纖維化，但其機制仍不清楚。因此本研究擬探討在不同甲狀腺素下對於硫代乙醯胺導致之肝纖維化的影響，並更進一步找到個別所扮演的機制。首先，大鼠利用硫代乙醯胺腹腔注射12週誘導為肝纖維化。之後分成三個組別研究，包括控制組、甲狀腺功能低下組及甲狀腺功能亢進組。甲狀腺功能低下大鼠使用局部甲狀腺摘除術。甲狀腺功能亢進大鼠則給予8週飲水添加甲狀腺素。組織病理學中，肝纖維化分數在甲狀腺功能低下組顯著較低 (1.62 ± 0.62)，而甲狀腺功能亢進組顯著較高 (2.6 ± 1.2)。肝體重比值甲狀腺功能亢進組 (4.38 ± 0.29) 顯著高於控制組 (4.08 ± 0.35) 與低下組 (3.86 ± 0.39)。肝組織中基質金屬蛋白酵素-2活化態顯著高於基質金屬蛋白酵素-2及-9的非活化態。同時間，肝組織基質金屬蛋白酵素-2活性在甲狀腺功能低下組 (49.18 ± 18.12) 顯著高於控制組 (18.73 ± 9.68)。肝組織基質金屬蛋白抑制物-1濃度在甲狀腺功能低下組 (3991.1 ± 1017.67) 與控制組 (2624.6 ± 812.64) 呈現顯著差異。肝臟轉型生長因子-β1濃度在甲狀腺功能低下組 (418.66 ± 102.46) 與亢進組 (251.43 ± 115.41) 及控制組 (212.28 ± 72.91) 間呈現顯著差異。而且，血清中基質金屬蛋白酵素-2活化態活性高於其他型態的基質金屬蛋白酵素，而在甲狀腺功能低下組顯著較高。結論，低濃度之甲狀腺荷爾蒙可透過間接提高基質金屬蛋白酵素的活性而幫助肝臟纖維化的回復，然而在高濃度的甲狀腺素則纖維化回復效果不明顯。

Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. In the formation of liver fibrosis, the activated hepatic stellate cell (HSC) turn into myofibroblast cell, and this process increases synthesis of collagen and decreases degradation. Some studies shows hypothyroidism could minimize liver damage and fibrosis in rats, but the mechanism still unclear. Therefore, the potential effect of thyroxin on fibrotic liver was investigated. Three groups including control, hypothyroid and hyperthyroid were studied. All rats were induced liver fibrosis by thioacetamide for 12 weeks. Hypothyroid rats were induced by partially thyroidectomy. Hyperthyroid rats were treated by eltroxin added in drinking water for 8 weeks. Under histopathology, liver fibrosis score showed significantly less in hypothyroid group (1.62 ± 0.62) and significantly higher in hyperthyroid group (2.6 ± 1.2). The ratio of liver weight/body weight in hyperthyroid group (4.38 ± 0.29) was significantly higher than both of control (4.08 ± 0.35) and hypothyroid groups (3.86 ± 0.39). The activity of liver matrix metalloproteinase (MMP)-2 active form showed significantly higher than activity of MMP-2 and -9 latent forms among three groups. Meanwhile, the activity of liver MMP-2 active form showed significantly higher in hypothyroid group (49.18 ± 18.12) compared to control group (18.73 ± 9.68). Liver tissue inhibitor of MMPs (TIMP)-1 concentration showed significant difference in hypothyroid group (3991.1 ± 1017.67) compared with control group (2624.6 ± 812.64). Liver transforming growth factor (TGF)-β1 concentration showed significant difference in hypothyroid group (418.66 ± 102.46) compared with hyperthyroid group (251.43 ± 115.41) and control (212.28 ± 72.91). Likewise, the serum MMP-2 active form showed higher activity level than other MMPs, and it showed significantly higher in hypothyroid group compared with other groups most of times. In conclusions, the low level of thyroid hormone could help the regression of liver fibrosis by indirectly promoted the activity of MMPs, whereas indistinctively regression of liver fibrosis with high level of thyroid hormone.
URI: http://hdl.handle.net/11455/12836
其他識別: U0005-0707201115170200
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