Study on expression and effect of pyroptosis in chronic diabetic wounds

WANG Yixiao; WANG Zihao; YANG Yunshu; GUAN Hao

doi:10.13276/j.issn.2097-1656.2024.08.004

Abstract：Objective To explore the expression and role of pyroptosis in chronic diabetic wounds.Methods One case of chronic diabetic wounds and one case of acute wounds were selected from the Department of Burns and Cutaneous Surgery,Xijing Hospital,Air Force Medical University in October 2023.The surgically excised wound edge tissue specimens were studied.The skin tissue was fixed,embedded in paraffin,and sectioned.HE staining and immunohistochemical staining of key molecules of pyroptosis,Caspase-1 and Gasdermin D,were performed.Human umbilical vein endothelial cells(HUVEC)were divided into blank group,disulfiram group,high glucose group,and high glucose+disulfiram group.Transwell experiments were performed to investigate the effect of high glucose and/or disulfiram treatment on HUVEC migration.Results HE staining showed mild hyperkeratosis of the wound edge tissue in acute non-diabetic wounds,with a small amount of inflammatory cell infiltration in the dermis and loose and orderly arrangement of collagen fibers.The epidermal layer of chronic diabetic wounds showed significant thickening,with obvious increase in inflammatory cell infiltration in the dermis and dense arrangement of collagen fibers.Immunohistochemical staining results suggested that pyroptosis-related molecules Caspase-1 and Gasdermin D were highly expressed in the dermal blood vessels and their surroundings in chronic diabetic wounds.Transwell experiments showed that high glucose significantly inhibited HUVEC migration(P＜0.01),while co-treatment with 30 μmol/L of disulfiram could significantly restore the inhibitory effect of high glucose on HUVEC migration(P＜0.01),indicating that disulfiram can significantly promote endothelial cell migration.Conclusion Endothelial pyroptosis is significantly activated in chronic diabetic wounds,and obstructing endothelial pyroptosis may become a key pathway to promote vascularization in diabetic wounds.