周邊動脈疾病(PAD，Peripheral arterial disease)是由於血管堵塞造成血流降低，以至於無法提供身體周邊組織足夠的血液灌流及代謝廢物，導致缺血區域喪失功能。目前尚未有穩定且持續的肢體缺血的大型動物模型適合測試外周動脈疾病(PAD)的新型血管新生療法。本研究通過不同的先決誘導條件測試不同蘭嶼豬下肢缺血誘導方式。在糖尿病誘導部分，本研究改良了過去前人誘導方式，再注射藥物過後施打葡萄糖溶液，發現能有效降低誘導死亡率及提升其成功率與維持時間，後續亦加入了老化的誘導與糖尿病同時進行，並將其應用於下肢缺血豬隻的誘導中，通過量化誘導後的下肢收縮壓、行為模式評估、血流回復及肌肉組織學，建立了適合用於評估治療的大型動物模型。結果顯示糖尿病豬隻結紮單側下肢的主要血管(IIA、IIV、EIA、EIV)及老化糖尿病豬隻結紮雙側EIA的方式，會在誘導後產生長時間的步態功能障礙、缺血症狀及肉眼可見的肌肉組織病變，本研究提供了PAD臨床前治療的大動物實驗平台，在後續血管新生治療方法上增加了從實驗室到臨床的轉化成功率。

Peripheral arterial disease (PAD) is caused by the reduction of blood flow due to vascular blockage, a symptom that makes it difficult to provide sufficient blood perfusion and metabolic wastes to the surrounding tissues of the body. Therefore, the ischemic area loses its function. Since there are currently no large animal models of stable and persistent limb ischemia which are suitable for testing novel angiogenic therapies for peripheral arterial disease (PAD), we used Lanyu pigs at different conditions to test various methods of inducing hind limb ischemia. This study improved the previous induction method of diabetes. The mortality is effectively reduced if the glucose solution is administered after injecting alloxan. Moreover, the success rate of diabetic induction is improved and the maintenance of hyperglycemia can be longer. In addition, D-galactose was used to induced aging of Lanyu pigs. To establish hind limb ischemia model, embolization and ligation were examined on external iliac artery (EIA), internal iliac artery (IIA), external iliac vein (EIV), internal iliac vein (IIV). Assessments of hind limb systolic blood pressure, behavioral patterns, blood flow recovery, and muscle histology were used to evaluate ischemic condition of hind limb in Lanyu pigs. Our results showed that ligating the unilateral IIA, IIV and the EIA, EIV in diabetes-induced pigs, or ligating of bilateral EIAs in diabetes-plus-aging-induced pigs will both bring prolonged gait dysfunction, ischemic symptoms, and obviously atrophy in gastrocnemius muscle and soleus muscle. Our study not only provides a large animal experimental platform for the preclinical treatment of PAD, but also increases the translational success rate from the laboratory to the clinic in subsequent angiogenesis treatments.

李易，DIB 於糖尿病下肢缺血小鼠治療之研究，國立成功大學生物科技研究所碩士論文，2016。

邱玟逸, 林柔君, 羅貽豪，下肢周邊動脈疾病，台灣老年醫學暨老年學雜誌，8，227-238，2013。

梁致文，蘭嶼豬糖尿病模式建立與傷口癒合研究，國立成功大學生物科技研究所碩士論文 ，2017。

許啟運，誘發生長豬隻第2型糖尿病：不同 TCF4 基因型之敏感性比較，國立宜蘭大學生物資源學院碩士論文，2015

詹秉鈞，蘭嶼豬下肢缺血動物模式之研究，國立成功大學生物科技與產業科學系研究所碩士論文，2019

鄭紫妃，改良之DIB膠於小鼠下肢缺血之治療，國立成功大學生物科技研究所碩士論文，2016。

簡崇美，糖尿病下肢缺血小鼠之治療，國立成功大學生物科技研究所碩士論文，2014。

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