| 研究生: |
徐維信 Hsu, Wei-Hsin |
|---|---|
| 論文名稱: |
脾臟全切除術早期活化肝臟部分切除大鼠肝再生之表現-藉由肝臟Activin-a表現之減少 Early activation of liver regeneration by splenectomy in hepatectomised rat via decreased expression of Activin-a of liver tissue |
| 指導教授: |
林炳文
Lin, Pin-Wen |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 分子醫學研究所 Institute of Molecular Medicine |
| 論文出版年: | 2005 |
| 畢業學年度: | 93 |
| 語文別: | 中文 |
| 論文頁數: | 50 |
| 中文關鍵詞: | 脾臟 、肝再生 、肝臟 |
| 外文關鍵詞: | activin, liver, spleen, liver regeneration, Il-6 |
| 相關次數: | 點閱:54 下載:1 |
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脾臟全切除加快肝臟再生此一現象已早被注意到,然而何種因素所造成至今依然沒有定論,是肝臟增生因子增加表現亦或抑制因子減少值得吾人探討。本研究以切除大鼠2/3 肝臟以引發肝臟再生之動物模式,術後以增生之全部肝臟重量與大鼠體重之比值相比較,實驗組(切除2/3 肝臟加上脾臟全切除) 於術後之第一天及第二天高於對照組(只切除2/3 肝臟)。以RT-PCR測定肝臟IL-6表現量,實驗組明顯低於對照組,血清學上IL-6濃度於實驗組大為降低。有學者發現來自脾臟TGF-ß1 與再生肝臟中的TGF-ß receptor II,會影響肝再生情形,本研究也可見到相似結果。以RT-PCR測定肝臟HGF (hepatic growth factor) mRNA的表現,在手術後一小時及兩小時實驗組高於對照組;而抑制性因子Activin-a方面,實驗組則於二、四、六小時明顯低於對照組;以Spot-denso 測定每一時間點之相對量, 以HGF與Activin-a之比值相比較,實驗組依然高於對照組,其中HGF在最早之時間點即已有所改變,可能與切除2/3 肝臟再加上脾臟全切除時造成之門脈血流動力學變化有關,但詳細機轉仍須詳加探討。在蛋白質層次上,以西方墨點也證實Activin-a表現量在對照組確實隨著時間點逐漸降低,而實驗組在相對時間點上更較對照組為低,參考過去文獻,TGF-ß1在部分切除肝臟後較手術前為高,然而其接受體卻降低,造成TGF- ß1 在肝臟再生早期“不敏感” (insensitivity),因此脾臟全切除加快肝臟再生的可能機轉上Activin-a似乎扮演更重要之角色,然而在臨床上仍須更詳盡的實驗數據及詳細機轉支持以茲運用。
Splenectomy enhanced liver regeneration was noticed for a long time. However, which factor was involved in this phenomenon is inconclusive. In this study, we used partial hepatectomised rat as a animal model to observe the expression of factors in liver regeneration. The ratio of regenerating liver and rat body weight at the time point 1 and 2 days in experimental group (partial hepatectmoy and splenectomy) is greater than that of control group (partial hepatectmy). Expression of RT-PCR of IL-6 in liver tissue of experimental group is lower than that of control group. ELISA for serum IL-6 confirmed above phenomenon. In previous research, TGF-ß 1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats. Results of this study confirm decreased expression of mRNA of TGF-ß 1 in experimental group than that of control group. It may be due to hemodynamic changes that induced HGF expression at early time point 1 and 2 hours when partial hepatectomy and splenectomy were done simultaneously. Messenger RNA expression of Activin-a in experimental group is lower than that of control group post operation 2、4 and 6 hours. Western blot showed decreased expression of Activin-a with time at control group that is more evident than experimental group at protein level. In previous papers, TGF-ß increased after hepatectomy but hepatocytes become insensitive to it in early phase due to down regulation of receptors on hepatocytes. Activin-a may play a important role for the enhancement of liver regeneration in the early period by splenectomy when TGF-ß signaling did not work. More data and detailed mechanism should be collected to unravel this problem for clinical application.
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