周邊動脈疾病(peripheral artery disease, PAD)困擾了全球超過兩億人，而糖尿病患者的高血糖容易使缺血症狀更嚴重及有更高的截肢率。先前實驗室已研發出能治療下肢缺血的膠體針劑DIW，然而我們尚未了解DIW的作用機制，因此此研究的目的為了解DIW在體內之作用。本實驗的下肢缺血動物模型為了使動物模型更接近臨床狀況，因此使用12月大的小鼠並誘導其患有一型糖尿病後手術誘導下肢缺血，在預計犧牲點犧牲小鼠後，對其腓腸肌進行分析化學組織染色以及免疫組織化學染色，結果顯示DIW治療後對於巨噬細胞的影響甚微，不管是在巨噬細胞浸潤面積還是極化方面。在血管生成方面，DIW表現出對微血管的生成並無影響，但其促進了動脈生成增加組織血流灌注，DIW治療也使的再生肌纖維的面積增，加速了肌纖維的再生，然而控制組的缺血肌肉內的神經纖維多於DIW組別，推測應該是控制組在缺血初期神經損害較嚴重才導致。DIW能幫助缺血組織動脈生成以及肌纖維的再生，最後達到治療下肢缺血的目的。

Lower extremity peripheral artery disease (PAD) impacts more than 200 million people in the world, and its incidence is closely associated with age and diabetes. Patients with diabetes have a higher risk for ischemic lesions and higher amputation rate. For the treatment of lower limb ischemia, we have developed DIW, which shows therapeutic efficacy against the exacerbation of hind limb ischemia in mice. However, the mechanism how DIW exerts its effect against ischemia still remains unknown. Therefore, the purpose of this study is to investigate the effect mechanisms of DIW in vivo. The hind limb ischemia murine model was surgically induced. To bring the model closer to the clinical situation, persistent hyperglycemia was induced in the mice in the experiment. To understand the effect of DIW on the ischemic muscle tissue, the ischemic gastrocnemius muscle was analyzed by histological staining and immunohistochemical staining. The results showed that DIW treatment had a slight effect on macrophages. In terms of angiogenesis, DIW appears to have no effect on the formation of microvascular, but it promotes arteriogenesis and increases tissue blood perfusion. DIW treatment also increases the area of regenerated muscle fibers and accelerates the regeneration of muscle fibers. However, there were more nerve fibers in the ischemic muscle in the control group than that of the DIW group. It is speculated that the nerve damage in the control group was more serious after ischemia. DIW can promote the growth of collateral arteries and muscle fiber regeneration in the ischemic tissue. Taken all together, DIW achieves the goal of slowing down contraction and reducing ischemic necrosis.

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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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