下肢動脈阻塞疾病 (lower extremity artery disease) 為下肢血管因硬化、栓塞或凝血機能異常等病變，造成血流無法正常供應身體組織養分與代謝，使得患處組織壞疽，若未即時給予治療，嚴重者將須面臨截肢命運。而此類患者多數同時患有糖尿病、高血壓等慢性疾病，易造成四肢末梢血管病變，其生理狀態長期處於高血糖，易促使組織中上皮細胞 (epithelial cell) 與肌纖維母細胞 (myofibroblast) 所分泌之血管內皮生長因子 (vascular endothelial growth factor) 與基質細胞衍生因子 (stromal cell-derived factor-1) 含量減少，減緩傷口自行癒合能力。而過去研究文獻指出細胞外基質 (extracellular matrix) ，如膠原蛋白、透明質酸、纖連蛋白等可促進細胞增殖與分化，清除氧化自由基，具有修復受損組織之功效，此外同時具有藥物控制釋放之功效。因此本研究目的在於以先前實驗室研發之治療性血管新生藥物DIB針劑為基礎，利用細胞外基質與抗凝血藥物作為主成分，以糖尿病小鼠下肢缺血動物模式為實驗平台篩選出更具療效性之促血管新生藥物，並藉由下肢外觀評分、血流訊號、組織切片染色與功能分析以評估其治療效果，盼研發出減緩下肢組織壞死之藥物。

Lower extremity arterial disease (LEAD) is a condition in which a medium to large artery that supplies oxygen-rich blood to the legs and feet becomes partially or completely blocked. Over a period of time, tissues in this area will be loss of function and necrosis. However, the majority of those people suffering from chronic diseases like diabetes and hypertension. In general, hyperglycemia will cause pathologic and functional changes in various target tissues. For example, the diabetic foot almost always occurs with critical limb ischemia caused by the peripheral arterial disease. This change makes the epithelial cell and myofibroblast secrete lesser vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1), which influenced the endothelial progenitor cells to slow down the remodeling of wound healing. Many investigations suggested that several extracellular matrix components such as collagen, hyaluronan and fibronectin not only can promote cell migration and proliferation, but metabolize reactive oxygen species and led to quick wound healing state. The objective of this research was based on the DIB gel, made by the BMT-lab to screen the best components from extracellular matrix and anticoagulant to treat the STZ-induced diabetic mice hind-limb ischemia animal model. We used photography to evaluate physical situation of the limb, and laser Doppler was utilized to detect the limb blood signaling. Finally we did some functional assays and sacrificed the mice to evaluate the effectiveness of modified DIB gel. We hope that the modified gel can improve quality of life and prevent major amputation.

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。

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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