细胞焦亡在糖尿病慢性创面中的表达与作用研究
Study on expression and effect of pyroptosis in chronic diabetic wounds
王奕潇 1王子昊 1杨云舒 2官浩2
作者信息
- 1. 空军军医大学:西京医院烧伤与皮肤外科,全军烧伤中心,陕西西安 710032;空军军医大学:基础医学院学员一大队,陕西西安 710032
- 2. 空军军医大学:西京医院烧伤与皮肤外科,全军烧伤中心,陕西西安 710032
- 折叠
摘要
目的 探索细胞焦亡在糖尿病慢性创面中的表达与作用.方法 选取2023年10月空军军医大学西京医院烧伤与皮肤外科收治的糖尿病慢性创面1例与普通急性创面1例,取术中切除的创缘组织标本进行研究,先将皮肤组织固定、石蜡包埋与切片,而后进行HE染色和细胞焦亡关键分子Caspase-1与Gasdermin D免疫组织化学染色,将人脐静脉内皮细胞(HUVEC)分为空白组、双硫仑组、高糖组与高糖+双硫仑组,Transwell实验检测高糖或/与双硫仑处理对HUVEC迁移影响.结果 HE染色观察发现急性非糖尿病创缘组织轻度角化增厚,真皮层局部有少量炎细胞浸润,胶原纤维排列较为疏松且规则有序;糖尿病慢性创缘皮肤表皮层显著增厚,真皮层中可见明显的炎细胞浸润增多,胶原纤维排列致密;免疫组织化学染色结果提示细胞焦亡相关分子Caspase-1与Gasdermin D在糖尿病慢性创缘中高表达且主要高表达于真皮层血管及其周围;Transwell实验结果表明高糖显著抑制HUVEC迁移(P＜0.01),而30 μmol/L双硫仑共处理能够显著恢复高糖所诱导的HUVEC迁移抑制效应(P＜0.01),提示抗焦亡抑制剂双硫仑能够显著促进HUVEC迁移.结论 血管内皮细胞焦亡在糖尿病慢性创面中显著激活,抗血管内皮焦亡可能成为促进糖尿病创面血管化的关键途径.
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.
关键词
糖尿病创面/细胞焦亡/慢性创面/双硫仑Key words
diabetic wounds/pyroptosis/chronic wounds/disulfiram引用本文复制引用
基金项目
国家自然科学基金青年科学基金(82302809)
中国高校产学研创新基金-健合医疗创面修复专项(2021JH030)
出版年
2024
国家科技期刊平台
NSTL
万方数据