心房顫動(atrial fibrillation)是臨床上常見的心律不整，且為一進行性式
(progressive)的疾病，通常以陣發性(paroxysmal)形式出現，逐漸發展成持續
性(persistent)及慢性/永久性(chronic or permanent)等形式。引起心房顫動的病
理機制目前仍沒有準確的原因，最終都會導致心房局部產生電訊號傳導迴路
(re-entry circuit)，阻礙心房細胞電訊號傳遞，使心房產生快速且不協調的活
動(focal ectopic activity)，降低心房收縮效率。由於不同步的心房收縮，也使
心室產生迅速且不規則的收縮，進而降低心臟整體輸送的功能。在本論文中，
我們利用高碘酸鈉(sodium metaperiodate)將多巴胺(dopamine)進行氧化，同
時聚合成導電性高分子聚多巴胺(polydopamine)並接枝於明膠(gelatin)上使
其交聯形成網狀之水膠結構，製備出具有黏性的導電性水膠貼片(Gel-PDA)，
將其貼附於心房顫動患部以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。在細胞實驗中，我們以鈣離子指示劑(Ca2+ indicator)
證實了導電性水膠貼片Gel-PDA具有協助心肌細胞的電訊號耦合及電訊號
傳遞能力。在動物實驗裡，我們將兩種轉基因之小鼠透過雜交建立自發性心
房顫動的模型後，將開發的導電性水膠貼片黏附至發生心房顫動處，並使用
心電圖、心臟超音波分析小鼠心臟功能的恢復。我們發現植入導電性水膠貼
片Gel-PDA後能有效延緩心臟功能惡化，包括了心房顫動現象的減輕及心臟
功能的維持。由以上實驗結果可知，本論文所開發出的導電性水膠貼片
Gel-PDA能夠對局部發生電訊號傳導迴路之心房進行電訊號整流，改善並延
緩持續惡化的心房顫動現象，進而同步心肌收縮，維持心臟功能，具有應用
於心房顫動疾病治療的潛能。

Atrial fibrillation (AF) is a clinically relevant arrhythmia. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then chronic or permanent form. During AF, rapid and uncoordinated atrial activity caused by the re-entry circuit leads to ineffective atrial contraction. In the incidence of AF, ventricular activations occur rapidly and irregularly, weakening cardiac contraction efficiency and causing clinical symptoms. In this study, a conductive hydrogel patch (Gel-PDA) was synthesized in the reaction of gelatin, dopamine (DA), and an oxidizing agent, sodium metaperiodate (NaIO4), resulting in the polymerization of DA to yield PDA and the conjugation of the PDA onto the backbone of gelatin, forming a Gel-PDA patch for treating fibrillating atria. The results of the in vitro study demonstrated that Gel-PDA enhanced electrical signaling propagation and electrical coupling between cardiomyocytes (CMs), as confirmed by the calcium staining. In the in vivo study, the Gel-PDA was implanted on the AF area of a transgenic mouse model; the results showed that a significant improvement of heart functions, such as reduced spontaneous arrhythmia and maintained fractional shortening. Overall, both in vitro and in vivo results clearly suggests that the Gel-PDA patch can synchronize cardiac contraction by electrically bridging isolated viable CMs within the re-entry circuit, maintaining the global heart function. The use of this novel conductive hydrogel patch may provide a new therapy strategy for the treatment of AF.

摘要 Ⅰ
目錄 III
圖錄 V
第一章 緒論 1
1.1 心房顫動 1
1.2 心房顫動之心電圖特徵 1
1.3 導電性高分子 3
1.4 聚多巴胺(polydopamine, PDA) 4
1.5 導電性水膠貼片(Gel-PDA) 5
1.6 研究動機與實驗目的 5
第二章 材料與方法 8
2.1 導電性水膠貼片Gel-PDA的製備 8
2.2 導電性水膠貼片Gel-PDA的導電度(Conductivity)分析 8
2.3 導電性水膠貼片Gel-PDA的黏滯力(Adhesive Strength)分析 8
2.4 導電性水膠貼片Gel-PDA的結構分析 8
2.5 控制組水膠Gel之交聯情形與交聯程度(Cross-linking Index)測試 9
2.6 導電性水膠貼片Gel-PDA的機械性質(Mechanical Properties)分析 9
2.7 導電性水膠貼片Gel-PDA的流變性質(Rheological Properties)分析 9
2.8 導電性水膠貼片Gel-PDA的膨潤度(Swelling Ratio)量測 10
2.9 導電性水膠貼片Gel-PDA的孔洞結構(Pore Size)分析 10
2.10 導電性水膠貼片Gel-PDA於體外之降解性測試 10
2.11 實驗動物 11
2.12 新生幼鼠心肌細胞(Neonatal Rat Cardiomyocytes)的分離與培養 11
2.13 導電性水膠貼片Gel-PDA的細胞存活率(Cytotoxicity)分析 11
2.14 導電性水膠貼片Gel-PDA的生物相容性(Cellular Compatibility)測試 12
2.15 新生鼠心肌細胞於Gel-PDA材料表面之同步跳動及鈣離子傳遞速率測量 12
2.16 導電性水膠貼片Gel-PDA於體內之生物相容性測試 12
2.17 導電性水膠貼片Gel-PDA於體內之H&E染色切片測試 12
2.18 建立小鼠心房顫動動物模型並進行導電性水膠貼片黏附 13
2.19 心電圖量測 13
2.20 執行心臟超音波 14
第三章 實驗結果與討論 14
3.1 Gel-PDA之導電度測試 14
3.2 Gel-PDA之黏滯力測試 16
3.3 Gel-PDA之結構分析 17
3.4 控制組水膠Gel之交聯情形與交聯程度(Cross-linking Index) 18
3.5 實驗組與控制組的導電度及黏滯力比較 20
3.6 Gel-PDA機械性質之分析 21
3.7 Gel-PDA流變性質之分析 22
3.8 Gel-PDA膨潤性質之分析 24
3.9 Gel-PDA孔洞結構之分析 24
3.10 Gel-PDA降解性質之分析 25
3.11 Gel-PDA生物相容性之分析 25
3.12 Gel-PDA細胞毒性之分析 26
3.13 新生鼠心肌細胞於Gel-PDA之同步跳動及鈣離子傳遞速率測量 26
3.14 Gel-PDA於體內之生物相容性測試 29
3.15 建立小鼠心房顫動動物模型 30
3.16 心電圖量測 31
3.17 執行心臟超音波 35
第四章 結論 37
參考文獻 38

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