首页|脱氢表雄酮通过抑制巨噬细胞戊糖磷酸途径促进糖尿病创面愈合

脱氢表雄酮通过抑制巨噬细胞戊糖磷酸途径促进糖尿病创面愈合

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目的 探讨脱氢表雄酮(dehydroepiandrosterone,DHEA)对糖尿病小鼠皮肤创面愈合的作用及机制。方法 高脂饲料联合链脲佐菌素诱导糖尿病小鼠模型,采用背部全层皮肤切创建立创面模型,小鼠随机分为普通创面模型组(NW)、糖尿病创面模型组(DW)和脱氢表雄酮干预组(DHEA),创面拍照并计算创面愈合率,RT-PCR检测创面组织和创面巨噬细胞炎症因子表达,检测创面巨噬细胞Dicer1和戊糖磷酸途径(pentose phosphate pathway,PPP)相关因子表达,提取创面巨噬细胞并与凋亡Jurkat细胞共培养,流式细胞术检测巨噬细胞吞噬凋亡细胞的吞噬率。结果 与NW组相比,DHEA组的创面愈合率、创面组织和创面巨噬细胞炎症因子表达、创面巨噬细胞吞噬凋亡细胞的吞噬率无差异(P>0。05);与DW组相比,DHEA组创面愈合加快,创面组织和创面巨噬细胞TNF-α、IL-6、IL-1β mRNA表达降低,IL-10、TGF-β mRNA表达增加,创面巨噬细胞吞噬凋亡细胞的吞噬率升高(P<0。01);与NW组相比,DW组创面巨噬细胞Dicer1 mRNA表达降低,PPP相关因子G6pdx、Taldo1、Pfkl、H6pd、Pgd、Aldoc1、Tkt mRNA表达增加(P<0。01);与DW组相比,DHEA组创面巨噬细胞Dicer1 mRNA表达无差异(P>0。05),PPP相关因子G6pdx、Taldo1、Pfkl、H6pd、Pgd、Aldoc1、Tkt mRNA表达减少(P<0。01)。结论 DHEA通过抑制巨噬细胞PPP,增强其吞噬功能,促进其分泌抗炎因子,抑制其分泌促炎因子,减轻创面炎症,进而加快糖尿病创面愈合。
Dehydroepiandrosterone promotes diabetic wound healing by inhibiting macrophage pentose phosphate pathway activity
This study was designed to study the effect and mechanism of dehydroepiandrosterone(DHEA)on diabetic wound healing in mice.High-fat feed combined with streptozotocin was utilized to induce diabetes and full-thickness incisional wounds were made on the back.The mice were randomly divided into normal wound group(NW),diabetic wound group(DW)and DHEA intervention group(DHEA).The wounds were photographed and the wound healing rates were calculated;RT-PCR was used to detect the expression of inflammatory factors in wound tissues and wound macrophages,and the expression of Dicer1 and pentose phosphate pathway(PPP)related factors in wound macrophages.Furthermore,wound macrophages phagocytosis of apoptotic Jurkat cells were measured by flow cytometry.Data showed that the wound healing rate,the expression of inflammatory factors and the phagocytosis rate were similar between the DHEA group and the NW group(P>0.05);compared with the DW group,the wound healing rate in the DHEA group was accelerated,the expression of TNF-α,IL-6 and IL-1β were decreased,the expression of IL-10 and TGF-β were increased,and the phagocytosis rate was increased(P<0.01);the expression of Dicer1 in wound macrophages of the DW group was lower than that in the NW group,and the expression of PPP-related factors G6pdx,Taldo1,Pfkl,H6pd,Pgd,Aldoc1 and Tkt were increased(P<0.01);the expression of Dicer1 between DW group and DHEA group was similar(P>0.05),and the expression of PPP-related factors G6pdx,Taldo1,Pfkl,H6pd,Pgd,Aldoc1 and Tkt were lower in the DHEA group(P<0.01).In conclusion,DHEA promotes diabetic wound healing by inhibiting macrophage pentose phosphate pathway activity.

DehydroepiandrosteroneDiabetic woundsMacrophagesPhagocytosisInflammatory response

陈宏、王素平、王佳薇、申子刚、陈利英、夏俊杰、符楚迪

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310000 杭州,中国人民解放军联勤保障部队第九〇三医院骨科

310000 杭州,中国人民解放军联勤保障部队第九〇三医院肿瘤科

310000 杭州,中国人民解放军联勤保障部队第九〇三医院内分泌科

400010,重庆市蚕业科学研究院

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脱氢表雄酮 糖尿病创面 巨噬细胞 吞噬功能 炎症反应

2024

免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
年,卷(期):2024.40(6)