Dimethyloxalylglycine Stabilizes HIF-1 alpha in Cultured Human Endothelial Cells and Increases Random-Pattern Skin Flap Survival In Vivo

作者:Shafighi Maziar*; Olariu Radu; Fathi Ali R; Djafarzadeh Siamak; Jakob Stephan M; Banic Andrej; Constantinescu Mihai A
来源:Plastic and Reconstructive Surgery, 2011, 128(2): 415-422.
DOI:10.1097/PRS.0b013e31821e6e69

摘要

Background: The goal of this study was to evaluate in vitro and in vivo the effects of up-regulation of the proangiogenic hypoxia inducible factor (HIF)-1 alpha induced by dimethyloxalylglycine on endothelial cell cultures and on skin flap survival.
Methods: Human umbilical vein endothelial cell cultures were exposed to hypoxic conditions, to dimethyloxalylglycine, and to cobalt chloride for up to 24 hours. Expression of HIF-1 alpha and vascular endothelial growth factor (VEGF) in cell culture media was analyzed. In vivo, 20 male Wistar rats were assigned randomly to either the treatment group (dimethyloxalylglycine intraperitoneal injection, n = 10) or the control group (saline intraperitoneal injection, n = 10). A dorsal skin flap was raised in all animals and sutured back into place. Flap survival was evaluated on postoperative day 7 by laser Doppler and digital planimetry.
Results: In vitro treatment of human umbilical vein endothelial cells during a 24-hour period showed a significant elevation of VEGF expression with dimethyloxalylglycine exposure (92 +/- 35 pg/mg total cellular protein) or hypoxia exposure (88 +/- 21 pg/mg total cellular protein) compared with controls (23 +/- 10 pg/mg total cellular protein) (p < 0.05 for both). In vivo experiments showed a significant decrease of flap necrosis in the treatment group animals versus controls (35.95 +/- 5.03 percent versus 44.42 +/- 5.18 percent, p < 0.05). The laser Doppler evaluation revealed significantly increased blood flow in the proximal two-thirds of the flap in the treatment group compared with the control group (p < 0.05).
Conclusion: Dimethyloxalylglycine treatment significantly increases VEGF and HIF-1 alpha expression in endothelial cell cultures and enhances skin flap survival in vivo in a rat model. (Plast. Reconstr. Surg. 128: 415, 2011.)

  • 出版日期2011-8