Effect of Roxadustat on Ischemic Skin Flaps in Diabetic Mellitus Rats

LIN Qiang; WANG Yinlong; WANG Song; WANG Dawei; YI Jiangnan; DU Gongzhi; HOU Huayi; TANG Di

doi:10.13730/j.issn.2097-2148.2025.10.001

Abstract：Objective To investigate the effects of Roxadustat on ischemic skin flaps in diabetic mellitus rats and explore its underlying mechanisms.Methods A total of 10 8-week-old male SD rats with successfully induced diabetes were randomly di-vided into normal saline group and Roxadustat group,with 5 rats in each.The rats in Roxadustat group were intraperitoneally in-jected with Roxadustat 25 mg/kg,and the rats in normal saline group were intraperitoneally injected with the same amount of normal saline every other day,7 d before operation and 0,2,4 and 6 days after operation,in total of 8 times.Two 5 cm× 1 cm symmetrical ischemic skin flaps were made on the back of rats,the microcirculation blood perfusion was evaluated by laser speckle flow imaging immediately after operation and 7 d after operation,and the skin flap survival rate at 7 d after operation was calcu-lated.The skin flap tissue and blood were collected at 7 d after operation,and some sections were taken and stained by hematoxylin-cosin(HE)and Masson to evaluate the his-topathological status of rats between two groups;Western blot was used to detect the expression of hypoxic inducible factor 1 alpha(HIF-1α),vascular endothelial growth factor(VEGF),platelet endothelial cell adhesion molecule CD31,type Ⅰ collagen(Col Ⅰ),Col Ⅲ and Col Ⅴ.The expression levels of interleukin 1 beta(IL-1β),IL-6 and tumor necrosis factor alpha(TNF-α)were determined by enzyme-linked immunosorbent assay;the contents of lactic acid,superoxide dismutase(SOD)and malondialdehyde(MDA)in skin flap and plasma were measured.The maximum tensile load of the skin flap incision was detected.Results Seven days after operation,compared with the normal saline group,the skin flap survival rate and the growth rate of skin flap blood perfusion significantly increased in the Roxadustat group(all P＜0.05),the skin flap had less in-flammatory cell infiltration,rich new blood vessels and tight collagen arrangement;the expression levels of HIF-1α,CD31,VEGF,Col I,Col Ⅲ and Col Ⅴ increased(all P＜0.05);the levels of inflammatory markers TNF-α,IL-6 and IL-1 β decreased(all P＜0.05);the lactate level and MDA level in plasma and skin flap tissue decreased,while SOD level increased(all P＜0.05);the maximum load of tensile force increased(P＜0.05).Conclusion Perioperative use of Roxadustat can improve the blood perfusion of diabetic mellitus ischemic skin flap,reduce the level of lactic acid and oxidative stress,reduce inflammatory re-sponse,promote angiogenesis and collagen deposition,and improve the survival rate and healing quality of the skin flap.