雄激素在缺氧诱导因子 (HIF)-1α诱导的血管生成和在大鼠模型中缺血性挑战皮瓣的存活中的作用。
The role of androgens on hypoxia-inducible factor (HIF)-1α-induced angiogenesis and on the survival of ischemically challenged skin flaps in a rat model.
机构信息
Department of Plastic, Reconstructive and Hand Surgery, University Hospital, Inselspital, University of Berne, Switzerland.
出版信息
Microsurgery. 2012 Sep;32(6):475-81. doi: 10.1002/micr.21996. Epub 2012 Jun 18.
BACKGROUND
Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1α promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis.
PURPOSE
This study investigates whether androgens stabilize HIF-1α in endothelial cells, and androgen depletion decreases VEGF concentrations and skin flap survival.
MATERIALS AND METHODS
Male human umbilical vein endothelial cells (HUVECs) were exposed to dihydrotestosterone (DHT) and HIF-1α expression was measured. In male Wistar rats, standardized proximally based random pattern dorsal skin flaps (3 × 9 cm) were raised 4 weeks after orchiectomy and sham operation, respectively (n = 10, each). Flap VEGF concentrations (immunohistochemistry), perfusion (Laser Doppler), and viability (digital planimetry) were measured.
RESULTS
DHT induced HIF-1α expression in HUVECs. Androgen depletion induced decreased VEGF expression (P = 0.003), flap perfusion (P < 0.05), and survival (44.4% ± 5.2%) compared to controls (35.5% ± 4.5%; P = 0.003).
CONCLUSION
In vitro, androgens may stimulate HIF-1α under normoxic conditions. In rats, androgen depletion decrease VEGF expression and flap survival.
背景
雄激素对血管生成的影响存在争议。缺氧诱导因子（HIF）-1α促进血管内皮生长因子（VEGF）的表达，刺激血管生成。
目的
本研究旨在探讨雄激素是否能稳定内皮细胞中的 HIF-1α，以及雄激素耗竭是否会降低 VEGF 浓度和皮瓣存活率。
材料与方法
将雄性人脐静脉内皮细胞（HUVECs）暴露于二氢睾酮（DHT）中，并测量 HIF-1α 的表达。雄性 Wistar 大鼠在去势和假手术后 4 周分别建立近端基于随机模式的背部皮肤皮瓣（3×9 cm）（n = 10，每组）。测量皮瓣 VEGF 浓度（免疫组化）、灌注（激光多普勒）和存活（数字绘图）。
结果
DHT 诱导 HUVECs 中 HIF-1α 的表达。与对照组相比（35.5% ± 4.5%；P = 0.003），雄激素耗竭导致 VEGF 表达（P = 0.003）、皮瓣灌注（P < 0.05）和存活（44.4% ± 5.2%）降低。
结论
在体外，雄激素可能在常氧条件下刺激 HIF-1α。在大鼠中，雄激素耗竭会降低 VEGF 表达和皮瓣存活率。
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