篇名 | Delivery of caveolin-1 gene into arterial walls of rabbits via an infiltrator angioplasty balloon catheter |
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卷期 | 12 |
並列篇名 | 利用滲入性血管整型氣球導管將caveolin-1基因注入白兔動脈管壁 |
作者 | 何鴻鋆 、 林玉俊 、 郭展延 、 丁紀台 、 林維文 、 鄭葳 |
頁次 | 001-014 |
關鍵字 | 動脈粥狀硬化 Caveolin-1 、 基因治療 、 局部注入方法 、 Atherosclerosis 、 Caveolin-1 、 Gene therapy 、 Local delivery system 、 TSCI |
出刊日期 | 201007 |
基因療法技術在治療動脈粥狀硬化疾病雖然快速的發展,然而將基因準確地送到治療目標,仍是血管基因治療的挑戰。我們以滲入性血管整型氣球導管(infiltrator angioplasty balloon catheter, IABC)將Caveolin-1 基因注入白兔主動脈管壁後,評估Caveolin-1 基因在注射部位的表現。首先將人類caveolin-1 基因及myc報導基因利用pcDNA 3.1 質體合成重組基因caveolin-1-myc,再利用滲入性血管整型氣球導管將此caveolin-1-myc 基因注射至白兔主動脈管壁,每三天注射一次,共注射兩週。在最後一次注射的兩週後將血管取下,以免疫組織化學染色法分析caveolin-1 蛋白質在注射位置的表現。由免疫螢光染色與西方點墨法的結果顯示caveolin-1-myc 基因成功表現在體外培養的細胞中。經由滲入性血管整型氣球導管注射後的兩週,以免疫組織染色發現Caveolin-1 蛋白質在白兔主動脈管壁中表現,而在注射部位並沒有上皮細胞或肌肉層之增生。本研究結果顯示滲入性血管整型氣球導管可做為基因治療心血管疾病的有效注入方式。
Gene therapy is a rapidly developing field with great potential for the treatment of atherosclerosis. Choosing the appropriate system for the precise delivery of genes into targeted plaques is still a challenging task for vascular gene therapists. We investigated the site-specific expression of the caveolin-1 gene within the aortic vessel walls in a rabbit model following local delivery of the gene via an infiltrator
angioplasty balloon catheter (IABC). The full-length untagged cDNA encoding human caveolin-1 was fused to the myc reporter gene using a pcDNA 3.1 plasmid.The caveolin-1-myc was then infused into the using a pcDNA 3.1 plasmid. The caveolin-1-myc was then infused into the aorta via IABC twice every three days for two weeks. The site-specific expression of caveolin-1 protein was analyzed by immunohistochemisty at two weeks after the last injection. Immunofluorescence analysis and Western blot indicated that caveolin-1-myc was present in the transfected cells. Caveolin-1 protein was detected in the medial layers of rabbit aorta for up to two weeks after IABC infusion and there was no intimal/medial thickening in the infusion area. IABC appears to be an effective gene delivery system for the treatment of cardiovascular diseases.