Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis
Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis
复制标题
DOI：
10.1177/1535370213492688
复制
发表时间：
2013-07-01
影响因子：
3.2
通讯作者：
Zagon, Ian S.
中科院分区：
文献类型：
--
作者：
McLaughlin, Patricia J.;Immonen, Jessica A.;Zagon, Ian S.
伤口愈合的延迟通常导致感染、慢性溃疡和可能的四肢截肢。伤口愈合不良是美国2300万糖尿病患者的主要并发症，经济和医疗负担要求新的伤口愈合治疗方法。先前的研究表明，局部应用溶解在保湿霜中的阿片类拮抗剂纳洛酮（NTX）可逆转链脲佐菌素诱导的1型糖尿病大鼠伤口闭合延迟。NTX的作用靶点是DNA合成和细胞增殖。在本研究中，评价肉芽组织以确定在糖尿病伤口中受损的特定细胞靶点，以及在NTX应用后增强的那些靶点。在正常和1型糖尿病大鼠背部全层皮肤伤口形成后3、5、8、10、15和20天，记录肥大细胞数量以及对成纤维细胞生长因子-2（FGF-2）、血管内皮生长因子（VEGF）和α平滑肌肌动蛋白（α-SMA）抗体免疫反应的新血管数量。糖尿病大鼠表现出伤口闭合延迟以及对损伤作出反应的肥大细胞数量减少，以及毛细血管中FGF-2、VEGF和α-SMA的时空表达延迟。局部NTX加速伤口闭合的速度和刺激的糖尿病大鼠肉芽组织内的血管生成因子的表达相对于对照动物接受生理盐水保湿霜。这些数据支持以下观察结果：在糖尿病条件下，新的生物途径受损，并且可以通过局部NTX调节以增强伤口愈合中的增殖事件。
Delays in wound healing often result in infection, chronic ulceration, and possible amputation of extremities. Impaired wound healing is a major complication of the 23 million people in the USA with diabetes, and financial and medical burdens are demanding new treatments for wound healing. Previous studies have demonstrated that topical application of the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in rats with streptozotocin-induced type 1 diabetes. A target of NTX's action is DNA synthesis and cell proliferation. In this study, granulation tissue was evaluated to ascertain the specific cellular targets that were impaired in diabetic wounds, as well as those that were enhanced following NTX application. Mast cell number as well as the number of new blood vessels immunoreactive to fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and alpha smooth muscle actin (alpha-SMA) antibodies were recorded at 3, 5, 8, 10, 15, and 20 days following creation of full-thickness dorsal cutaneous wounds in normal and type 1 diabetic rats. Diabetic rats displayed delays in wound closure as well as a reduction in the number of mast cells responding to the injury, and delays in the spatial and temporal expression of FGF-2, VEGF, and alpha-SMA in capillaries. Topical NTX accelerated the rate of wound closure and stimulated expression of angiogenic factors within granulation tissue of diabetic rats relative to control animals receiving saline in moisturizing cream. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be modulated by topical NTX to enhance proliferative events in wound healing.