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作者(中文):呂亭萱
作者(外文):Lu, Ting-Hsuan
論文名稱(中文):利用 MRI 可追踪具黏性水膠片對心肌細胞進行電耦合治療心房顫動
論文名稱(外文):Using an MRI-Traceable, Adhesive, Conductive Hydrogel Electrically Coupling of Cardiomyocytes for Treating Atrial Fibrillation
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
陳松青
陳俊男
劉培毅
口試委員(外文):Chang, Yen
Chen, Sung-Ching
Chen, Chun-Nan
Liu, Pei-Yi
學位類別:碩士
校院名稱:國立清華大學
系所名稱:化學工程學系
學號:109032502
出版年(民國):111
畢業學年度:110
語文別:中文
論文頁數:62
中文關鍵詞:心房顫動導電性高分子核磁共振超順磁氧化鐵心肌細胞
外文關鍵詞:Atrial fibrillationConductive hydrogelSuperparamagnetic iron oxideMagnetic Resonance ImagingCardiomyocyte
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心房顫動(atrial fibrillation)為臨床上最常見之持續性心臟節律異常,是一種心臟電傳導系統的疾病。該疾病之病理特徵為快速紊亂的心房跳動,通常是因為心房局部區域快速放電所誘發複雜的心電迴路(re-entrant circuit),造成心房與心室喪失同步收縮,導致一系列的心臟功能惡化。現有的藥物治療有很大的限制,原因包括藥物間相互作用和不良反應,甚至可能再次誘發心律失常。因此手術治療已逐漸成為有利的替代方案,但現行的治療方式安全性和有效性仍不完善乃至於有併發症的風險,完全治癒的患者數量有限,而完善的臨床治療需求尚未被滿足。心臟貼片是對心臟疾病提供治療的一種有效方法,可直接黏附於心臟上進行長時間治療,另外我們希望藉由無創的方式觀察材料植入身體後之變化,避免再次手術的創傷,同時也有助於減少實驗中不必要的動物犧牲。本論文中擬研發一核磁共振影像可追蹤(magnetic resonance imaging (MRI)-traceable)之導電性水膠貼片,不僅協助心肌傳遞電訊號,同時利用非侵入性的方式觀察水膠貼片於體內的變化。我們將具黏性及自我摻雜特性之導電高分子聚多巴胺(polydopamine, PDA)接枝於明膠(gelatin, Gel)上,並摻混MRI顯影劑超順磁氧化鐵粒子(superparamagnetic iron oxide, SPIO),製備出MRI可追蹤具黏性水膠片(Cit-SPIO Gel-PDA patch)應用於小鼠心房顫動之心臟功能改善。在動物實驗中,我們使用轉基因小鼠建立自發性心房顫動動物模型,以正中胸骨切開術將水膠貼片黏附於小鼠的右心室。在手術完成後,不僅能夠利用核磁共振影像系統以非侵入性的方式監測體內的水膠,此外根據心電圖及心臟超音波對心臟功能的評估結果顯示,Cit-SPIO Gel-PDA patch能對局部發生電訊號傳導迴路之心房進行整流,減輕心房顫動的症狀,有效延緩心臟功能的惡化,具有應用於心房顫動臨床治療的潛力。
Atrial fibrillation (AF) is caused by rapid, complex and multiple re-entrant circuit that move randomly around the atria. This process results in rapid and irregular atrial activations, reducing the efficiency of cardiac contraction. Medications have gradually been taken the place by non-pharmacological therapies because of the limitation by their lack of complete effectiveness, the interactions and adverse effects of drugs, and even an increased risk of ventricular proarrhythmic; however, the safety and effectiveness of non-pharmacological are less than perfect and they can be used on a limited range of patients. The effective and adequate treatment of AF remains an unmet medical need. Hydrogels are being studied for various potential cardiac uses, and conductive hydrogel patches may be able to restore the functions of infarcted tissue by synchronizing atrial propagation and enhancing atrial-ventricular coupling to prevent further adverse structural and functional remodeling of the atrial tissues. The use of noninvasive imaging modalities to track cardiac patches after implantation to reduce the number of experimental animals. Magnetic resonance imaging (MRI) is well suited to the serial and real-time in vivo measurement owing to its diverse functional sequences, large penetration depth and safety. Motivated by the need for novel treatment modalities, an MRI-traceable, adhesive, conductive hydrogel that is synthesized by a series of reaction in which DA undergoes oxidative self-polymerization to yield conductive polydopamine (PDA) and can be conjugated onto the backbone of gelatin; meanwhile, SPIO, as the imaging agent, is embedded in the synthesized hydrogel network, forming an MRI-traceable, adhesive, conductive hydrogel patch (Cit-SPIO Gel-PDA patch) that can integrate a re-entry current and synchronize cardiomyocyte contraction to treat AF. This method has the extra advantage of non-invasively tracking in real-time enabling the non-invasive tracking in real time of changes in the patch structure. Cit-SPIO Gel-PDA patch may provide a new means of treating AF.
摘要 I
Abstract II
目錄 III
圖表目錄 VI
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 2
1.3 導電性高分子 3
1.4 聚多巴胺 3
1.5 黏性水膠貼片 4
1.6 磁共振造影成像 5
1.7 超順磁性氧化鐵奈米粒子 6
1.8 研究動機與實驗目的 7
第二章 材料與方法 11
2.1 對照組水膠(Gel)的製備 11
2.2 導電性水膠貼片(Gel-PDA)的製備 11
2.3 親油性氧化鐵粒子(OA-SPIO)的製備 11
2.4 親油性(OA-SPIO)轉換成親水性氧化鐵粒子(Cit-SPIO) 12
2.5 MRI可追蹤之導電性水膠貼片的製備 13
2.6 對照組水膠之特性分析 13
2.7 黏性水膠貼片之特性分析 14
2.8 氧化鐵粒子之特性分析 14
2.9 MRI可追蹤之導電性水膠貼片之性質分析(Cit-SPIO Gel-PDA ) 16
2.10 實驗動物 18
2.11 新生幼鼠心肌細胞(Neonatal Rat Cardiomyocytes)的分離與培養 19
2.12 體外實驗 (in vitro studies) 19
2.12.1 氧化鐵粒子的細胞存活率分析 19
2.12.2 不同水膠的細胞存活率分析 19
2.12.3 新生幼鼠心肌細胞於不同材料表面之同步跳動情形 20
2.13 建立自發性心房顫動動物模型 20
2.14 體內實驗 (in vivo studies) 21
2.14.1 不同水膠於體內之生物相容性測試及切片組織染色 21
2.14.2 小鼠心房顫動動物模型的建立 22
2.14.3 左心室黏附水膠貼片動物實驗 22
2.14.4 心電圖量測 23
2.14.5 心臟超音波的量測 23
2.14.6 程式化電刺激誘發心律不整敏感性測試 24
2.14.7 體內磁共振造影成像分析 26
第三章 結果與討論 27
3.1 對照組水膠(Gel)之相關分析 27
3.2 黏性水膠貼片(Gel-PDA)之相關分析 28
3.3 氧化鐵粒子(Cit-SPIO)之相關分析 32
3.4 MRI可追蹤之導電性水膠貼片(Cit-SPIO Gel-PDA)之相關分析 37
3.5 不同水膠貼片之性質綜合分析 41
3.6 不同水膠貼片於體內和體外實驗之綜合分析 43
第四章 結論 54
參考文獻 55
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