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系統識別號 U0026-2207201417314800
論文名稱(中文) 探討血管受傷模式下凝血酶調節素在血管平滑肌細胞上扮演的角色
論文名稱(英文) The Role of Thrombomodulin in Vascular Smooth Muscle Cells Following Vascular Injury
校院名稱 成功大學
系所名稱(中) 生物化學暨分子生物學研究所
系所名稱(英) Department of Biochemistry and Molecular Biology
學年度 102
學期 2
出版年 103
研究生(中文) 林盈里
研究生(英文) Ying-Li Lin
學號 s16001094
學位類別 碩士
語文別 英文
論文頁數 53頁
口試委員 指導教授-施桂月
口試委員-吳華林
口試委員-林淑華
口試委員-江美治
中文關鍵字 凝血酶調節素  血管平滑肌細胞  血管壁病變 
英文關鍵字 Thrombomodulin  smooth muscle cell  vascular dysfunction 
學科別分類
中文摘要 血管平滑肌細胞(vascular smooth muscle cell)為血管壁的基質細胞,其主要功能在於調控維持正常血壓。血管平滑肌細胞同時也參與在許多因血管壁病變所導致的疾病。血管平滑肌細胞具有細胞型態轉變的能力,可由收縮態轉為具增生能力的合成態。細胞周圍環境發生改變,例如血管受傷病變時會調控血管平滑肌細胞產生型態轉變。凝血酶調節素(Thrombomodulin,TM)為細胞上的穿膜醣蛋白,在抗凝血、細胞之間黏著、抗發炎中扮演重要角色。先前的研究顯示,凝血酶調節素表現在人類動脈粥狀硬化血管及小鼠頸動脈結紮所誘發新生內膜層的平滑肌細胞。因此,為了要探討在血管受傷的情況下,凝血酶調節素在血管平滑肌細胞上所扮演的角色,我們使用平滑肌細胞特異剔除凝血酶調節素基因小鼠,進行小鼠頸動脈結紮誘發血管病變。另外,Ki67免疫螢光染色及末端脫氧核苷酸轉移酶脫氧尿苷三磷酸切口末端標記試驗分別用來探討,當體內血管平滑肌細胞上TM缺失時,是否影響細胞生長或細胞凋亡。平滑肌細胞特異剔除凝血酶調節素基因小鼠在頸動脈結紮四周後,其新生內膜層的形成以及新生內膜/中層增生比率,較野生型小鼠皆有減少的情形。此外,在平滑肌細胞特異剔除凝血酶調節素基因小鼠血管新生內膜層的血管平滑肌細胞,表現出較低的細胞增生能力和較高的細胞凋亡情形。整體而言,在血管受傷病變的情況下,血管平滑肌細胞上的凝血酶調節素可能調控細胞增生和移行。此研究提出一個新證據來強調當血管受傷病變時,血管平滑肌細胞上的凝血酶調節素在病理上所扮演的角色。
英文摘要 Vascular smooth muscle cells (VSMCs), the stromal cells of the vascular wall, have the main function in regulating blood pressure. They are also involved in many pathological changes in the vascular wall. VSMCs are flexible and have the ability to transition from a contractile state to a proliferative-migratory synthetic state during a process known as phenotypic switching. Changes in local environment such as vascular dysfunction may regulate VSMCs phenotype switching. Thrombomodulin (TM), a glycoprotein expressed on the cell surface, plays an important role in anti-coagulation, cell-cell adhesion and anti-inflammation. It was previously reported that TM was expressed in VSMCs of human atherosclerotic arteries and in the neointima in carotid artery ligation (CAL) in mice. To explore the role of TM in VSMCs during vascular injury, we used CAL to induce vascular dysfunction in smooth muscle cell-specific deficient mice (SM22CreTMflox/flox mice). In addition, Ki67 immunofluorescence staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to investigate whether deficiency of TM in VSMCs affects cell growth or cell death in vivo respectively. SM22CreTMflox/flox mice revealed a decrease in neointima formation at 4 weeks post CAL as well as a reduced neointima/media ratio compared with wild type mice. Futhermore, SM22CreTMflox/flox mice displayed poor proliferation but increased apoptosis of neointimal VSMCs. In summary, TM may modulate proliferation and migration in VSMCs during vascular injury. This finding may provide a new evidence to emphasize the pathological role of TM in VSMCs following vascular injury.
論文目次 Abstract in Chinese 1
Abstract in English 2
Acknowledgement 3
Content 4
Figure Contents 5
Abbreviation 6
Instruments 7
Reagents and Chemicals 9
Introduction 12
Specific Aim 17
Materials and Methods 18
Results 27
Conclusion 31
Discussion 32
Figures 36
References 46
Author’s resume 52
Appendixes 53

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