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博碩士論文 etd-0827107-112806 詳細資訊
Title page for etd-0827107-112806
論文名稱
Title
Bone morphogenetic protein-2 在肝臟纖維化中的角色與功用
The role and effect of bone morphogenetic protein-2 in liver fibrosis
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
63
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2007-07-13
繳交日期
Date of Submission
2007-08-27
關鍵字
Keywords
肝臟纖維化、骨形成蛋白
liver fibrosis, Bone morphogenetic protein-2
統計
Statistics
本論文已被瀏覽 5699 次,被下載 1167
The thesis/dissertation has been browsed 5699 times, has been downloaded 1167 times.
中文摘要
骨形成蛋白 (bone morphogeneticprotein, BMP)是轉型生長因子(TGF-β)的家族成員之ㄧ。它們的功能可以調控細胞增生,細胞分化,與骨質新生。根據研究顯示,作為TGF-β的拮抗物,BMP-2在組織纖維化中或許有扮演抑制的角色。這個實驗的目的是要觀察BMP-2在由膽道結紮或是四氯化碳所誘發肝臟纖維化過程中的表現與變化,並且更進一步的利用基因傳送來表現BMP-2,來觀察它對於肝臟纖維化的調控作用。結果顯示出在膽道結紮或是注射四氯化碳的小鼠中,它們的血清生化數據都有明顯的升高,而且TGF-β, α型平滑肌肌動蛋白, 第一型膠原蛋白的表現都有明顯增加,但是在膽道結紮後第7天與第14天或是注射四氯化碳2周與4周後,BMP-2在基因與蛋白質的表現都是明顯下降的。給予膽道結紮或是四氯化碳所誘發肝臟纖維化的小鼠基因治療,在BMP-2基因轉殖後,發炎反應與肝臟受損的情況都有降低,根據這些觀察,BMP-2在肝臟纖維化過程中扮演重要的角色。
Abstract
Bone Morphogenetic proteins (BMPs) belong to transforming growth factor beta (TGF-β) superfamily. They regulate cell proliferation, cell differentiation, and bone morphogenesis. Previous evidence suggests that BMP-2, as an antagonist of TGF-β, may play an inhibitory role in tissue fibrogenesis. The aim of this study is to examine the expression profile of BMP-2 in fibrotic livers and to test whether BMP-2 gene delivery could alleviate or reverse the liver fibrogenesis models in mice including bile duct ligation (BDL) or carbon tetrachloride (CCl4) model. The results showed that the AST, ALT, and bilirubin levels in sera and the expression of TGF-β, α-smooth muscle actin, type I collagen in livers were significantly up-regulated by BDL surgery or CCl4 administration. After BDL, the hepatic BMP-2 mRNA and protein levels in mice decreased at 7 and 14 days after surgery. Similarly, the hepatic BMP-2 mRNA and protein levels in mice decreased at day 14 and 28 after CCl4 administration. BMP-2 gene delivery alleviated the inflammation and the liver injury caused by BDL or CCl4 exposure. These findings strongly suggest that BMP-2 is involved in the pathogenesis of liver fibrosis. Moreover, BMP-2 supplementation may facilitate a novel strategy for treatment of liver fibrosis.
目次 Table of Contents
Contents……………………………………………………...1
Abbreviations………………………………………………..2
Abstract in Chinese………………………………………….3
Abstract in English…………………………………………..4
Introduction…………………………………………………..5
Materials and Methods……………………………………..10
Results……………………………………………..…..…….19
Discussion……………………………………………....……26
Figures……………………………………………………….32
References………………………………………...…………55
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