Promotion of Random Flap Neovascularisation in Rats with Diabetes Using Botulinum Toxin Type A Through the HIF-1α/VEGF Pathway

Hong-Jie Yan,1,* Fang-Ming Lin,2,* Jing-Jing Li,1 Hao Qin,1 Yi-He Wang,1 Chuan-Hua You1 1Department of Plastic and Cosmetic Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, People’s Republic of China; 2Department of Vascular Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, 570100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuan-Hua You, Department of Plastic and Cosmetic Surgery, The First Affiliated Hospital of Hainan Medical University, No. 31 of Longhua Street, Longhua District, Haikou, 570102, People’s Republic of China, Tel +8615120793168, Fax +86-1083161294, Email youchuanhua3063@163.comObjective: This study aimed to investigate the effects of botulinum toxin type A (BoTA) on the neovascularisation of diabetic flaps through the factor-1alpha (HIF-1α)/vascular endothelial growth factor (VEGF) pathway.Methods: A total of 60 male Wistar rats (250– 300 g) were randomly divided into 4 groups. Group A consisted of normal rats receiving saline, Group B received BoTA, Group C were diabetic rats treated with saline, and Group D were diabetic rats treated with BoTA. Random-pattern dorsal skin flaps (3× 9 cm) were created, and saline or BoTA was injected at proximal, mid and distal regions. Ten days later, orthotopic flap transplantation was performed. After 7 days, flap survival rate, haematoxylin–eosin (H&E) staining, and the mRNA expression of HIF-1α and VEGF were evaluated.Results: Flap survival area significantly increased in Group B compared to Group A (P < 0.05), and in Group D compared to Group C (P < 0.05). The highest neovascular density was observed in Group B (P < 0.05), while the lowest was in Group C (P < 0.05). No significant difference was found between Groups A and D. Reverse transcription polymerase chain reaction (RT-PCR) showed that HIF-1α and VEGF expression levels were highest in Group B, followed by Groups A, D, and C (P < 0.05).Conclusion: BoTA promotes flap survival and neovascularisation in diabetic rats by enhancing HIF-1α and VEGF expression. These results suggest a potential therapeutic role of BoTA in improving flap outcomes in diabetic patients.Keywords: botulinum toxin type A, flap, diabetes, factor-1alpha