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作者(中文):高翔宇
作者(外文):Gao, Xiang-Yu
論文名稱(中文):探討導電性生物工程補綴片協助心臟電訊號傳遞及其心臟梗塞後治療之評估
論文名稱(外文):A Bio-Engineered Conductive patch Improves Electrical Propagation and Cardiac Function After Myocardial Infarction
指導教授(中文):宋信文
指導教授(外文):Sung, Hsing-Wen
口試委員(中文):張燕
李伯偉
口試委員(外文):Chang, yan
Li, Po-Wei
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生物醫學工程研究所
學號:106038466
出版年(民國):109
畢業學年度:108
語文別:中文
論文頁數:30
中文關鍵詞:心肌梗塞心律不整導電性生物工程補綴片
外文關鍵詞:myocardial infarctionarrhythmiaBio-Engineered Conductive patch
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心血管疾病目前是世界上主要的死亡原因之一,而急性心肌梗塞(acute myocardial infarction, AMI)是一種常見的心臟疾病,其最常見的成因為冠狀狹窄或阻塞導致的心肌細胞死亡。冠狀動脈是供給心臟血液的動脈,在發生心肌梗塞後,心肌細胞因無法透過冠狀動脈獲得足夠的氧氣和養分而死亡。心肌細胞死亡後在心肌梗塞區域被纖維化的成疤組織(scar tissue)所取代。纖維化組織中死亡的心肌細胞無法與正常心肌細胞的進行電訊號的傳遞,無法形成連接從而導致心律失常。在本論文中,我們提出了一種新型的導電性生物工程補綴片,將導電性高分子聚3-氨基-4-甲氧基苯甲酸(poly-3-mino-4-methoxybenzoic acid, PAMB)接枝於明膠海綿(gelfoam)上製備出具生物相容性的導電性高分子補綴片,期望將材料與細胞結合並縫合於心臟梗塞患部幫助心肌電訊號的傳遞,使心臟同步收縮,達到心臟功能恢復之目的。在體外實驗里,我們發現補綴片具有讓心肌細胞粘附、幫助細胞維持跳動頻率的作用。同時我們以鈣離子指示劑Ca2+ indicator 在熒光顯微鏡中觀察心肌細胞的同步收縮情形與相關電訊號傳遞通道蛋白的表現,證實了導電性生物工程補綴片具有協助心肌細胞的電訊號耦合與電訊號傳遞。由以上實驗結果表明,本論文所開發出的導電性生物工程補綴片,藉由PAMB上的羧基和氨基使得導電性補綴片在生理環境中具有穩定的導電度,能有效傳遞心肌細胞間的電訊號,具有應用於心臟梗塞後治療的潛能。
Cardiovascular diseases are the leading cause of death in the world, and acute myocardial infarction (AMI) is a common heart disease, most commonly due to myocardial cell death due to coronary stenosis or obstruction. Coronary arteries are the arteries that supply blood to the heart. After myocardial infarction, cardiomyocytes (CMs) cannot get enough oxygen and nutrients through the coronary arteries. The proliferating fibroblasts causes scar formation in and around the infarction. The nonconductive nature of the collagen scar tissue causes electrically uncoupling of viable CMs in the infarct region. In this work, we evaluated the conductivity and efficacy of a newly synthesized conductive poly-3-amino-4-methoxybenzoic acid (PAMB)-gelfoam (G) patch to support CM viability and function in vitro. The results of the in vitro study demonstrated that PAMB-G patch were biocompatible and provided a suitable surface for cell attachment. Meanwhile, PAMB-G patch enhanced electrical signaling propagation and electrical coupling between cardiomyocytes, as confirmed through the calcium signaling analysis. The use of this novel bio-engineered conductive patch may provide a new therapy strategy for the treatment of MI.
目錄
摘要 1
目錄 3
圖錄 5
第一章 緒論 7
1.1 心肌梗塞 7
1.2 心律不整 7
1.3 心臟組織工程 8
1.4 細胞因子強化補綴片 9
1.5 治療心肌梗塞所面臨的難題 9
1.6 導電性高分子 10
1.7 導電性高分子聚3-胺基-4-甲氧基苯甲酸(3-amino-methoxybenzoic acid, PAMB) 11
1.8 研究動機與實驗目的 11
第二章 材料與方法 14
2.1 PAMB-Gel補綴片的製備 14
2.2 PAMB-Gel補綴片導電度分析 14
2.3 PAMB-Gel補綴片結構分析 14
2.4 PAMB-Gel補綴片表面結構分析 14
2.5 PAMB-Gel補綴片溶脹行為分析 14
2.6 PAMB-Gel補綴片機械性質分析 15
2.7 PAMB-Gel補綴片自我摻雜特性分析 15
2.8 新生幼鼠心肌細胞的分離與培養 15
2.9 PAMB-Gel補綴片生物相容性之測試 15
2.10 新生鼠心肌細胞於PAMB-Gel補綴片鈣離子訊號量測 16
2.11 新生鼠心肌細胞於 Gel PAMB 材料表面之電訊號傳遞分析 16
2.12 新生鼠心肌細胞於PAMB-Gel補綴片鈣離子訊號量測 16
第三章 實驗結果與討論 17
3.1 PAMB-Gel補綴片導電度測定 17
3.2 PAMB-Gel補綴片之結構分析 18
3.3 PAMB-Gel補綴片表面結構分析 18
3.4 PAMB-Gel補綴片的溶脹行為分析 20
3.5 PAMB-Gel補綴片機械性質分析 20
3.6 PAMB-Gel補綴片自我摻雜特性分析 22
3.7 新生鼠心肌細胞於PAMB-Gel補綴片上連接蛋白熒光分析 23
3.8 新生鼠心肌細胞於PAMB-Gel補綴片Ca2+瞬時傳遞分析 24
3.9 新生鼠心肌細胞於PAMB-Gel補綴片上之電訊號傳遞分析 26
3.10 新生鼠心肌細胞於PAMB-Gel補綴片鈣離子訊號量測 27
第四章 結論 28
參考文獻 29
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