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  • 學位論文

Aspirin和Ticlopidine抑制人類臍帶內皮細胞所表現的 趨化激素 (單核球趨化激素-1、介白質素-8)

Aspirin and Ticlopidine Inhibit Monocyte Chemoattractant Protein-1、IL-8 and E-selectin Expression

指導教授 : 楊沂淵
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摘要


動脈硬化所引起的併發症,例如心肌損傷、中風以及周邊血管疾病,在世上是主要引起疾病和和死亡率的原因。有研究顯示在動脈硬化發生時,細胞激素和吸附分子會促進發炎細胞的趨化。單核球趨化蛋白-1 (MCP-1) 是動脈硬化損傷中最早發展的一個主要因子,而CXC細胞激素 (IL-8) 是個有效吸引單核球到血管內皮,進而扮演增加單核球的角色。另外,單核球吸附至內皮細胞對發炎反應是一個重要步驟,其中包含吸附分子 (E-選擇素) 的誘導。在本篇研究中,我們探討aspirin和ticlopidine表現在人類臍帶靜脈內皮細胞 (HUVEC) 的影響。結果顯示,aspirin以及ticlopidine藉由RT-PCR和流式細胞分析儀抑制TNF-α [10ng/ml] 所誘導MCP-1、 IL-8以及E-選擇素的表現。利用分析MTT試驗顯示,aspirin和ticlopidine的抑制作用並不會減少HUVEC生存率。這些結果顯示利用TNF-α刺激HUVEC,aspirin以及ticlopidine能夠抑制MCP-1、 IL-8和E-選擇素的釋放,則可能提供另一項的治療機制。

並列摘要


Atherosclerosis and its complications, such as myocardial infraction, stroke, and peripheral vascular disease, remain major causes of morbidity and mortality in the worldwide. Studies demonstrated that chemokines and adhesion molecules are involved in the pathogenesis of atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiation and development of atherosclerotic lesion. The CXC chemokine, IL-8 is a powerful trigger for firm adhesion of monocyte to vascular endothelium, indicating a potential role for this chemokine in monocyte rescruitment. Monocyte adhesion to endothelial cells is crucial for inflammation, involving induction of E-selectin. In this study, we investigated the effects of aspirin and ticlopidine on MCP-1、IL-8 and E-selectin expression in human umbilical vein endothelial cells (HUVEC). Aspirin and ticlopidine inhibit TNF-α [10 ng/ml]-induced MCP-1、IL-8 and E-selectin expression as detected by RT-PCR and flow cytometery. In addition, the inhibitory effects of aspirin and ticlopidine were not due to decreased HUVEC viability, as assessed by MTT test. These results suggest that aspirin and ticlopidine inhibit MCP-1、IL-8 and E-selectin release in HUVEC stimulated by TNF-α, thereby providing an additional mechanism for therapeutic effects of aspirin and ticlopidine.

並列關鍵字

HUVEC MCP-1 IL-8 E-selectin

參考文獻


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