去铁胺喷剂促进Ⅲ度烧伤慢性创面愈合的调节机制OA
The regulatory mechanism of deferoxamine spray in promoting the healing of chronic wounds in third-degree burns
目的 探究去铁胺喷剂(deferoxamine,DFO)对Ⅲ度烧伤慢性创面愈合的影响及其作用机制.方法 通过细胞毒性检测筛选出可用于后续实验的DFO喷剂浓度.通过成管实验检测DFO喷剂对人脐静脉内皮细胞(HUVECs)生成血管能力的影响.通过FerroOrange探针、活性氧(reactive oxygen species,ROS)检测以及丙二醛测定,评估DFO喷剂对细胞内亚铁离子(Fe2+)积累、细胞内ROS生成及脂质氧化反应的影响.将SD雄性大鼠随机分为对照组和DFO喷剂治疗组(DFO组),使用台式超温控烫伤机制备大鼠Ⅲ度烧伤慢性创面模型,并通过定时观察记录创面愈合情况.采用苏木精-伊红和马松染色评估组织学变化.免疫组化染色观察血小板内皮细胞黏附分子1(CD31)、铁蛋白(Ferritin)和长链酰基辅酶A合成酶4(long-chain acyl-CoA synthase 4,ACSL4)蛋白表达水平.结果 浓度5 μg/mL的DFO喷剂能够显著促进HUVEC细胞生成血管,并且显著抑制细胞内Fe2+积蓄(P＜0.001),降低细胞内ROS生成(P＜0.01),减少细胞内脂质氧化反应(P＜0.001).使用DFO喷剂治疗的Ⅲ度烧伤大鼠慢性创面,能够更快恢复皮肤完整结构(P＜0.05),沉积更多胶原蛋白(P＜0.001).与对照组相比,DFO喷剂组的大鼠创面组织中CD31表达水平显著升高(P＜0.001),Ferritin表达水平显著下降(P＜0.001),ACSL4表达水平显著下降(P＜0.001).结论 DFO喷剂明显促进SD大鼠Ⅲ度烧伤慢性创面愈合,其作用机制可能为促进血管再生,阻止细胞内Fe2+积蓄,降低ROS水平,减少脂质过氧化反应,抑制铁死亡通路表达从而促进创面愈合.
Objective To explore the effects and its mechanism of deferoxamine spray on the healing process of chronic wounds from third-degree burns.Methods Screening the concentration of deferoxamine spray suitable for subsequent experiments through cytotoxicity testing.The tube formation assay was used to assess the effect of deferoxamine spray on the angiogenic ability of human umbilical vein endothelial cells(HUVECs).The FerroOrange detection probe kit,reactive oxygen species(ROS)detection kit,and malondialdehyde(MDA)measurement kit were used to evaluate the effects of deferoxamine spray on intracellular ferrous ion(Fe2+)accumulation,intracellular reactive oxygen generation,and lipid oxidation reactions.The male SD rats were randomly divided into a control group and a deferoxamine spray treatment group.A chronic wound model of third-degree burns was established using a desktop hyperthermic burn machine,and the healing of the wounds was recorded through timed observations.Hematoxylin-Eosin and Masson staining were used to assess the re-epithelialization of the wound tissue and local collagen deposition,respectively.Immunohistochemical staining was performed to observe the expression of PECAM-1(CD31),ferritin,and long-chain acyl-Coa synthetase 4(ACSL4)proteins.Results A 5 μg/mL concentration of deferoxamine spray could significantly promote the angiogenesis of HUVECs,and significantly inhibited intracellular Fe2+accumulation(P＜0.001),reduced intracellular ROS generation(P＜0.01),and decreased intracellular lipid oxidation reactions(P＜0.001).In the chronic wounds of third-degree burn rats treated with deferoxamine spray,the restoration of skin integrity was faster(P＜0.05),and more collagen was deposited(P＜0.001).Compared to the control group,the expression of CD31 in the wound tissue of the deferoxamine spray treatment group was significantly increased(P＜0.001),while ferritin expression and ACSL4 expression were significantly decreased(P＜0.001).Conclusion Deferoxamine spray significantly promotes the healing of chronic wounds from third-degree burns in SD rats,and its mechanism may involve promoting angiogenesis,preventing intracellular iron accumulation,reducing ROS generation,decreasing lipid peroxidation reactions,and inhibiting the expression of ferroptosis pathways,thereby facilitating wound healing.
柴朗捷;李琴;郭亮;黄姜龙
武汉大学中南医院整形美容科(武汉 430071)湖北航天医院医疗美容科(湖北孝感 432000)武汉大学中南医院整形美容科(武汉 430071)湖北航天医院医疗美容科(湖北孝感 432000)||武汉市中医医院整形美容科(武汉 430050)
临床医学
去铁胺Ⅲ度烧伤慢性创面愈合铁死亡
DeferoxamineThird-degree burnsChronic wound healingFerroptosis
《医学新知》 2025 (4)
394-401,8
航天医疗健康科技集团有限公司科研项目(2022YK12)
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