背景:糖尿病足溃疡(DFU)是一种常见的糖尿病并发症,与残疾和生活质量降低有关。可用的治疗剂不足以对抗DFU的传播。在这里,我们的目标是调查高度平衡的影响,糖基化终产物(AGE)-交联破坏剂,DFU的愈合。
方法:STZ诱导Wistar大鼠糖尿病,四周后,脚上有伤口。平衡(10mg/kg)口服给药14天,每3天测量伤口大小。行为测试,即,热板和足迹测试,进行评估感觉功能和步态。收集血液以评估HbA1c,血清AGEs,MDA和NOX1。收集组织以评估组织学变化和NF-κB的表达。iNOS,TNF-α,VEGF和EGF。在随后的一组类似设计的实验中,作为成膜凝胶局部应用alagebalance。
结果:系统平衡治疗加速了糖尿病伤口的愈合,改善感觉功能和步态,和改善组织学变化。它还降低了AGEs的血清水平,MDA和NOX1,以及NF-κB的组织表达,iNOS,TNF-α,并在糖尿病大鼠中增加VEGF和EGF。局部平衡导致类似的有益效果,即加速糖尿病伤口愈合,改善伤口组织学变化,NF-κB和iNOS的表达减少,VEGF增加。
结论:我们的研究结果表明,糖尿病患者在治疗DFU时重新调整平衡,以加速愈合过程并改善临床结局。
BACKGROUND: Diabetic foot ulcer (DFU) is a common diabetic complication associated with disability and reduced quality of life. Available therapeutics are not sufficient to combat the spread of DFU. Here we aim to investigate the impact of alagebrium, an advanced glycation end product (AGE)-crosslink breaker, on the healing of DFU.
METHODS: Diabetes was induced in Wistar rats by STZ, and after four weeks, wound was induced on the foot. Alagebrium (10 mg/kg) was administered orally for 14 days, and wound size was measured every 3 days. Behavioral tests i.e., hot plate and footprint tests, were performed to assess sensory function and gait. Blood was collected to assess HbA1c, serum AGEs, MDA and
NOX1. Tissue was collected to assess histological changes and expression of NF-κB, iNOS, TNF-α, VEGF and EGF. In a subsequent set of experiments with similar design, alagebrium was applied topically as a film-forming gel.
RESULTS: Systemic alagebrium treatment accelerated the healing of diabetic wound, improved sensory functions and gait, and ameliorated histological changes. It also reduced serum levels of AGEs, MDA and
NOX1, and the tissue expression of NF-κB, iNOS, TNF-α, and increased VEGF and EGF in diabetic rats. Topical alagebrium led to similar beneficial effects i.e., accelerated diabetic wound healing, improved wound histological changes, reduced expression of NF-κB and iNOS and increased VEGF.
CONCLUSIONS: Our findings suggest repurposing of alagebrium for the management of DFU to accelerate the healing process and improve the clinical outcomes in diabetic patients.