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Updated: Jun 9, 2025
Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia
Published on: November 17, 2014
Hypoxia-Inducible Factor-1α Potentiates Multiterritory Perforator Flap Survival by Augmenting Vascular Endothelial
Xiuan Zeng1, Yunfei Xie2, Tao Guo2
1From the The Affiliated Baiyun Hospital of Guizhou Medical University, GuiYang, PR China.
Background:
Hypoxia-inducible factor-1α (HIF-1α), regulated by prolyl hydroxylase, plays a central role in tissue adaptation to ischemia. This study investigates the impact of HIF-1α on angiogenesis in the Choke II zone of multiterritory perforator flaps.
Methods:
Ninety male Wistar rats were allocated into 3 groups, with 30 rats in each group: the dimethyloxalylglycine (DMOG) group, the 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1) group, and the normal saline (NS) group. All rats underwent multiterritory perforator flap surgeries on their dorsal side. Subsequently, they received intraperitoneal injections of DMOG (40 mg/kg), YC-1 (10 mg/kg), and normal saline on postoperative days 1, 2, and 3, respectively. After treatment, angiogenesis in the Choke II zone of the flap on day 7 was observed through transillumination tests and lead oxide/gelatin x-ray angiography. Histological features were determined using hematoxylin and eosin staining, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) in the Choke II region of the flap was assessed via immunohistochemistry and western blotting.
Results:
Compared to the YC-1 and NS groups, the DMOG group exhibited significant angiogenesis, resulting in a denser vascular network in the Choke II zone of the flap. The DMOG group showed significantly higher microvessel density in the Choke II zone than the YC-1 and NS groups (7.10 ± 0.99 vs 24.30 ± 3.65; 14.30 ± 2.40 vs 24.30 ± 3.65, both P<0.05). Additionally, the DMOG group demonstrated higher expression of VEGF and HIF-1α in the flaps than the other groups (P < 0.05).
Conclusions:
In summary, HIF-1α enhances the expression of VEGF, promoting angiogenesis in the Choke II zone of the multiterritory perforator flap, thus increasing the survival area.
