Department of Neural & Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Exp Biol Med (Maywood). 2013 Jul;238(7):733-43. doi: 10.1177/1535370213492688. Epub 2013 Jun 20.
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 (α-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 α-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.
伤口愈合延迟通常会导致感染、慢性溃疡，并可能导致四肢截肢。在美国，有 2300 万人患有糖尿病，他们是伤口愈合不良的主要人群，这给他们带来了巨大的经济和医疗负担，因此需要寻找新的治疗方法。先前的研究表明，将阿片受体拮抗剂纳曲酮（NTX）溶解在保湿霜中局部应用，可逆转链脲佐菌素诱导的 1 型糖尿病大鼠的伤口闭合延迟。NTX 的作用靶点是 DNA 合成和细胞增殖。在这项研究中，我们评估了肉芽组织，以确定糖尿病伤口中受损的特定细胞靶标，以及 NTX 应用后增强的细胞靶标。在正常和 1 型糖尿病大鼠背部全层皮肤创伤形成后第 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）抗体呈免疫反应的新血管数量。糖尿病大鼠表现出伤口闭合延迟，以及对损伤反应的肥大细胞数量减少，以及 FGF-2、VEGF 和毛细血管中α-SMA 的时空表达延迟。与接受保湿霜中生理盐水的对照动物相比，局部 NTX 加速了糖尿病大鼠伤口闭合的速度，并刺激了肉芽组织中血管生成因子的表达。这些数据支持这样一种观点，即在糖尿病条件下，一种新的生物学途径受损，可以通过局部 NTX 来调节，以增强伤口愈合过程中的增殖事件。
