Local injection of deferoxamine improves neovascularization in ischemic diabetic random flap by increasing HIF-1α and VEGF expression.
Local injection of deferoxamine improves neovascularization in ischemic diabetic random flap by increasing HIF-1α and VEGF expression.
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通过增加HIF-1α和VEGF的表达，地下defreoxamine局部注射可改善缺血性糖尿病随机皮瓣的新血管化。
DOI：
10.1371/journal.pone.0100818
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cui L
中科院分区：
文献类型：
--
作者：
Wang C;Cai Y;Zhang Y;Xiong Z;Li G;Cui L
虽然去铁胺（DFO）的全身给药是保护正常缺血皮瓣和糖尿病伤口的实验模型，其对糖尿病皮瓣缺血使用局部注射的效果仍然未知。探讨局部注射DFO改善链脲佐菌素（STZ）诱导的糖尿病小鼠缺血随意皮瓣存活的可行性。在125只小鼠上制作缺血随意皮瓣。将动物分为DFO治疗组（n = 20）、PBS治疗组（n = 16）和未治疗组（n = 16）。 术后第7天观察存活面积、血管密度、血管内皮生长因子（VEGF）和缺氧诱导因子-1 α（HIF-1α）的表达。与两个对照组相比，DFO治疗组皮瓣的存活率显著提高，局部血液灌注和毛细血管密度增加。荧光活化细胞分选（FACS）分析表明，DFO处理小鼠的全身Flk-1+/CD 11b −内皮祖细胞（EPCs）显著增加。此外，VEGF和HIF-1α的表达不仅在糖尿病皮瓣组织中增加，而且在高糖和低氧条件下培养的真皮成纤维细胞中也增加。局部注射DFO可通过提高糖尿病小鼠缺血皮瓣中HIF-1α和VEGF的表达，增加EPC动员，从而保护糖尿病小鼠缺血皮瓣的存活。
Although the systemic administration of deferoxamine (DFO) is protective in experimental models of normal ischemic flap and diabetic wound, its effect on diabetic flap ischemia using a local injection remains unknown. To explore the feasibility of local injection of DFO to improve the survival of ischemic random skin flaps in streptozotocin (STZ)-induced diabetic mice. Ischemic random skin flaps were made in 125 mice. Animals were divided into the DFO-treated (n = 20), PBS-treated (n = 16) and untreated (n = 16) groups. Surviving area, vessel density, and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were evaluated on the seventh day after local injection. The viability of DFO-treated flap was significantly enhanced, with increased regional blood perfusion and capillary density compared with those in the two control groups. Fluorescence-activated cell sorting (FACS) analysis demonstrated a marked increase in systemic Flk-1+/CD11b− endothelial progenitor cells (EPCs) in DFO-treated mice. Furthermore, the expression of VEGF and HIF-1α was increased not only in diabetic flap tissue, but also in dermal fibroblasts cultured under hyperglycemic and hypoxic conditions. Local injection of DFO could exert preventive effects against skin flap necrosis in STZ-induced diabetic mice by elevating the expression of HIF-1α and VEGF, increased EPC mobilization, which all contributed to promote ischemic diabetic flap survival.
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10.1073/pnas.0906670106
发表时间：
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