Immonen Jessica A, Zagon Ian S, McLaughlin Patricia J
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
Adv Wound Care (New Rochelle). 2014 Jun 1;3(6):419-427. doi: 10.1089/wound.2014.0543.
Type 2 diabetes (T2D) is associated with impaired cutaneous wound healing and can result in ulceration, infection, and/or amputation. More than 25 million people in the United States have T2D and are vulnerable to epithelial-related complications. Current therapies are limited in their efficacy. New treatments for full-thickness cutaneous wounds that focus on underlying diabetic pathways are needed. Topical application of the opioid receptor antagonist naltrexone (NTX) dissolved in cream reverses delayed wound closure in type 1 diabetic rat by the acceleration of reepithelialization and enhancement of angiogenesis and remodeling. NTX blocks the opioid growth factor (OGF)-OGF receptor (OGFr) axis and upregulates DNA synthesis and cell proliferation. To investigate whether NTX is an effective therapy for T2D wound closure, genetically obese mice () and normal C57Bl/6J mice received full-thickness cutaneous wounds. Wounds (5 mm in diameter) were treated topically three times daily with 10 M NTX or sterile saline dissolved in cream and photographed every 2 days. Wounds in mice treated with saline were 11-92% larger than those in normal mice throughout the 2-week observation. Topical NTX therapy in T2D mice reduced the residual wound size by 13-30% between days 8 and 14 relative to diabetic mice receiving saline. Reepithelialization and DNA synthesis, as analyzed by epithelial thickness and BrdU labeling indexes, respectively, were accelerated in NTX-treated wounds. These data suggest that the OGF-OGFr axis plays a role in epithelial-related complications of T2D and that blockade of this pathway by NTX may be an effective treatment for wound repair.
2型糖尿病（T2D）与皮肤伤口愈合受损有关，可导致溃疡、感染和/或截肢。美国有超过2500万人患有T2D，易患与上皮相关的并发症。目前的治疗方法疗效有限。需要针对潜在糖尿病途径的全层皮肤伤口新治疗方法。局部应用溶解于乳膏中的阿片受体拮抗剂纳曲酮（NTX）可通过加速再上皮化、增强血管生成和重塑来逆转1型糖尿病大鼠伤口愈合延迟。NTX阻断阿片生长因子（OGF）-OGF受体（OGFr）轴并上调DNA合成和细胞增殖。为了研究NTX是否是治疗T2D伤口愈合的有效疗法，将遗传性肥胖小鼠（）和正常C57Bl/6J小鼠制作全层皮肤伤口。用10μM NTX或溶解于乳膏中的无菌盐水每天局部处理伤口3次，每2天拍照。在整个2周观察期内，用盐水处理的小鼠伤口比正常小鼠伤口大11%-92%。与接受盐水的糖尿病小鼠相比，T2D小鼠局部应用NTX治疗在第8天至14天期间将残余伤口大小减少了13%-30%。分别通过上皮厚度和BrdU标记指数分析，NTX处理的伤口中再上皮化和DNA合成加速。这些数据表明OGF-OGFr轴在T2D的上皮相关并发症中起作用，并且NTX阻断该途径可能是伤口修复的有效治疗方法。
