Minicircle-VEGF165의 Sonoporation을 이용한 당뇨쥐의 상처치료

Abstract

The purpose of this study is to examine the efficiency of sonoporation with minicircle DNA for the skin wound healing in diabetic mice. Minicircle DNA containing the human VEGF165 was constructed and tested in vitro. Diabetes was induced in 2-week old male C57BL/6J mice via streptozotocin (STZ) injection. 6 mm circular skin wounds were made on the dorsal of mice. After the subcutaneous injection of the minicircle DNA at the edge of the wound, the mice were exposed to the ultrasound irradiation for the sonoporation. Wound area was analyzed for 12 days after sonoporation. Blood perfusion and angiogenesis were evaluated using laser Doppler imaging and CD31 immunostaining. Re-epithelialization was assessed by histochemical analysis using hematoxylin and eosin staining. Accelerated wound closure was observed in the mice which were treated with the sonoporation of the minicircle-VEGF165, which is constituent with the markedly increased skin blood perfusion and CD31 expression. Histological analysis revealed that the minicircle-treated wound tissues showed fully restored normal architecture in contrast with the non-treated diabetic controls with the markedly edematous and chaotic morphology. Ultrasound mediated gene therapy with the minicircle-VEGF165 was effective in healing of the skin wound of the diabetic mice.