皮肤性病诊疗学杂志2024，Vol.31Issue(3)：147-156,10.DOI:10.3969/j.issn.1674-8468.2024.03.001
1,25(OH)2D3对小鼠皮肤创伤愈合的作用及机制研究
Study on the effects of 1,25(OH)2D3 on cutaneous wound healing and the underlying mechanisms in mice
摘要
Abstract
Objective To study the role of 1,25(OH)2D3 in cutaneous wound healing and the underlying mechanisms in mice.Methods Forty 5-week-old male C57BL/6 mice were randomly divided into 5 groups,i.e.,wound,wound+vitamin D receptor(VDR)inhibitor,wound+vi-tamin D receptor(VDR)agonist,wound+vitamin D(VD)powder and normal controls.The wound healing rates were calculated according the photographs of wound size taken at different time points.At the 9th day of wound,ELISA was used to measure serum levels of 1,25(OH)2D3.In addition,wound edge tissue was taken for HE staining and immunohistochemi-cal staining of VDR and CD31.Finally,expression levels of both mRNA and proteins for VDR,Notch1,TNF-α,IL-17A,IL-17F and IL-22 were assessed using real-time quantitative PCR and Western Blot,respectively.Results At the 9th day of wound,the levels of serum 1,25(OH)2D3 and cutaneous VDR and CD31 expression were decreased,while expression levels of TNF-α,IL-17A,IL-17F and IL-22 were increased in the wounded skin compared to the normal controls(P＜0.05).Expression levels of Notch1 did not differ significantly between the normal and wounded skin(P＞0.05).Compared with the untreated wounded skin,treatments with either VDR agonist or VD powder significantly increased wound healing rate,serum 1,25(OH)2D3 levels and expres-sion levels of cutaneous VDR,CD31 and Notch1,while decreasing cutaneous TNF-α,IL-17A,IL-17F and IL-22 expression(P＜0.05).VDR inhibitor increased expression levels of cutaneous TNF-α and IL-22 protein(P＜0.01 vs.untreated wound),without significant changes in wound healing rate,serum 1,25(OH)2D3 levels,mRNA for cutaneous VDR,CD31,Notch1,TNF-α,IL-17A,IL-17F and IL-22,and protein levels of Notch1,IL-17A and IL-17F.Moreover,the re-sults of HE staining showed that treatments with either VDR agonist or VD powder significantly de-creased inflammatory infiltration in the wounded tissue,while increasing angiogenesis along with dense connective tissue in the dermis and almost complete re-epithelialization in the epidermis.Conclusion In a mouse model of full thickness skin excision wound,1,25(OH)2D3 promotes wound healing,possibly by inhibition of the expression of TNF-α,IL-17A,IL-17F,and IL-22,and increases in the expression of Notch1 receptor and VDR,and angiogenesis.关键词
骨化三醇/维生素D受体/Notch1受体/皮肤创伤愈合/炎症因子Key words
calcitriol/vitamin D receptor/Notch1 receptor/skin wound healing/cyto-kines引用本文复制引用
母兴语,何小解,黄诒洁,杭倩如,翁于格,丁艳..1,25(OH)2D3对小鼠皮肤创伤愈合的作用及机制研究[J].皮肤性病诊疗学杂志,2024,31(3):147-156,10.基金项目
海南省重点研发计划项目(ZDYF2020147) （ZDYF2020147）
