Topical fentanyl stimulates healing of ischemic wounds in diabetic rats 局部芬太尼麻醉可以促进糖尿病大鼠缺血性伤口的愈合

Abstract Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth‐promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Z ucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the L eptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho‐platelet derived growth factor receptor‐β ( PDGFR ‐β) were visualized by CD 31‐, lymphatic vessel endothelium‐1, protein gene product 9.5‐ and anti‐phospho PDGFR ‐β‐immunoreactivity, respectively. Nitric oxide synthase ( NOS ) and PDGFR ‐β signaling were analyzed using W estern immunoblotting. Results Fentanyl significantly promoted wound closure as compared to phosphate‐buffered saline ( PBS ). Histology scores were significantly higher in fentanyl‐treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR ‐β signaling as compared to PBS . Phospho‐ PDGFR ‐β co‐localized with CD 31 co‐staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR ‐β signaling are associated with fentanyl‐induced tissue remodeling and wound healing.