McLaughlin Patricia J, Cain Jarrett D, Titunick Michelle B, Sassani Joseph W, Zagon Ian S
Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania.
Department of Orthopaedics and Rehabilitative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania.
Adv Wound Care (New Rochelle). 2017 Sep 1;6(9):279-288. doi: 10.1089/wound.2016.0725.
Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Topical application of 0.03% NTX cream accelerates diabetic wound closure. Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.
在美国，糖尿病影响着超过2900万人，导致医疗费用接近2450亿美元。这些患者中约15%会患上慢性、不愈合的足部溃疡（糖尿病足溃疡[DFU]），若不治疗，可能导致截肢。目前治疗DFU的方法费用高昂、有显著副作用，且常常导致患者依从性差。本文描述了一种新的局部治疗方法，该方法通过靶向潜在的异常糖尿病途径来加速皮肤伤口修复并改善病情。在使用1型糖尿病大鼠的临床前研究中，比较了阿片受体拮抗剂纳曲酮（NTX）和重组人血小板衍生生长因子（Regranex）的疗效。将背部皮肤伤口分别局部用0.03% NTX、Regranex或单独的保湿霜治疗。监测伤口闭合情况、DNA合成和细胞因子产生。1型糖尿病大鼠局部使用NTX的伤口闭合率与Regranex相当。通过BrdU掺入法测量，局部使用NTX可加速DNA合成，增加肥大细胞，并增强血小板衍生生长因子（PDGF）和血管内皮生长因子（VEGF，血管生成标志物）的表达。与用赋形剂处理的伤口相比，Regranex对DNA合成、肥大细胞和VEGF表达几乎没有影响，且仅能暂时增加PDGF表达。两种治疗方法均未改变成纤维细胞生长因子的表达。局部应用0.03% NTX乳膏可加速糖尿病伤口愈合。在临床前研究中，使用0.03% NTX乳膏阻断阿片生长因子（OGF）-OGF受体（OGFr）轴与标准治疗相当，并且为糖尿病伤口治疗提供了一种安全、廉价且有效的替代方法。
