College of Nursing, University of Florida, Gainesville, FL 32610, USA.
Biol Res Nurs. 2010 Apr;11(4):336-44. doi: 10.1177/1099800409346333. Epub 2009 Dec 22.
Many chronic wounds fail to heal with conventional therapy, resulting in disability and impaired quality of life. New technologies using recombinant growth factors, autologous growth factors, or bioengineered skin-tissue substitutes have been shown to be effective, but these treatments are costly. An effective, low-cost treatment to improve healing of chronic wounds is needed. The molecular environment of chronic wounds, like many other chronic inflammatory diseases, contains abnormally high levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1beta]) and matrix metalloproteinases (MMPs), which impair normal wound healing. In animal models and clinical studies of ulcerative diseases, doxycycline, an inexpensive and Food and Drug Administration (FDA)-approved antibiotic, appears to inhibit members of the MMP superfamily like MMPs and TNF-alpha-converting enzyme (TACE). This article provides an overview of the roles of MMPs and intrinsic tissue inhibitors of metalloproteinases (TIMPs) in wound healing and the damaging effects of chronically elevated levels of MMPSs in chronic wounds. It also explores the use of topical doxycycline, a synthetic MMP inhibitor (MMPI), to enhance healing of chronic wounds.
许多慢性创伤无法通过常规治疗愈合，导致残疾和生活质量受损。使用重组生长因子、自体生长因子或生物工程皮肤组织替代物的新技术已被证明是有效的，但这些治疗方法成本高昂。需要一种有效且低成本的治疗方法来改善慢性创伤的愈合。与许多其他慢性炎症性疾病一样，慢性创伤的分子环境中含有异常高水平的促炎细胞因子（肿瘤坏死因子 [TNF]-α 和白细胞介素 [IL]-1β）和基质金属蛋白酶（MMPs），这会损害正常的伤口愈合。在溃疡性疾病的动物模型和临床研究中，多西环素是一种廉价且获得美国食品和药物管理局 (FDA) 批准的抗生素，似乎可以抑制 MMP 超家族成员，如 MMP 和 TNF-α 转化酶 (TACE)。本文概述了 MMPs 和内源性金属蛋白酶抑制剂 (TIMPs) 在伤口愈合中的作用，以及慢性升高的 MMPs 在慢性创伤中的破坏性影响。它还探讨了局部使用多西环素（一种合成 MMP 抑制剂 [MMPI]）来增强慢性创伤的愈合。
