Plastic Surgery Department, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Plastic Surgery Division, The University of Texas Medical Branch, Galveston, Texas, USA.
Plastic Surgery Division, The University of Texas Medical Branch, Galveston, Texas, USA; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
J Invest Dermatol. 2014 Jan;134(1):237-246. doi: 10.1038/jid.2013.301. Epub 2013 Jul 18.
Little is known about the impact of hyperbaric oxygen treatment (HBOT) on matrix metalloproteinase (MMP) production in pre-existing high-oxidant wounds. This study aimed to investigate whether HBOT modulates reactive oxygen species (ROS) and MMP regulation in ischemic wound tissue. Using a validated ischemic wound model, Sprague-Dawley rats were divided into four groups for daily treatment: HBOT, N-acetylcysteine (NAC), HBO and NAC, and control (normoxia at sea level). High levels of inducible nitric oxide synthase (iNOS), gp91-phox, and 3-nitrotyrosine were detected in ischemic wounds, indicating high-oxidant stress. HBOT not only increased antioxidant enzyme expression, such as Cu/Zn-superoxide dismutase, catalase, and glutathione peroxidase, but also significantly decreased pro-oxidant enzyme levels, such as iNOS and gp91-phox, thereby decreasing net oxygen radical production by means of negative feedback. This effect was blocked by NAC treatment in ischemic wounds. HBO-treated ischemic wounds also manifested reduced phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase, and c-Jun, indicating downregulation of mitogen-activated protein kinases (MAPKs). Furthermore, HBOT decreased the expression of several MMPs while simultaneously increasing tissue inhibitor of MMP (tissue inhibitor of metalloproteinase 2). These results indicate that HBOT acts via the ROS/MAPK/MMP signaling axis to reduce tissue degeneration and improve ischemic wound healing.
关于高压氧治疗（HBOT）对已有高氧化应激伤口中基质金属蛋白酶（MMP）产生的影响知之甚少。本研究旨在探讨 HBOT 是否调节缺血性伤口组织中的活性氧（ROS）和 MMP 调节。使用经过验证的缺血性伤口模型，将 Sprague-Dawley 大鼠分为四组进行每日治疗：HBOT、N-乙酰半胱氨酸（NAC）、HBO 和 NAC 以及对照（海平面常氧）。在缺血性伤口中检测到诱导型一氧化氮合酶（iNOS）、gp91-phox 和 3-硝基酪氨酸的高水平，表明存在高氧化应激。HBOT 不仅增加了抗氧化酶的表达，如 Cu/Zn-超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶，而且还显著降低了促氧化剂酶的水平，如 iNOS 和 gp91-phox，从而通过负反馈减少净氧自由基的产生。这种作用被缺血性伤口中的 NAC 治疗阻断。接受 HBO 治疗的缺血性伤口也表现出细胞外信号调节激酶 1/2、c-Jun N 端激酶和 c-Jun 的磷酸化减少，表明丝裂原激活蛋白激酶（MAPKs）下调。此外，HBOT 降低了几种 MMP 的表达，同时增加了组织金属蛋白酶抑制剂（MMP 组织抑制剂 2）。这些结果表明，HBOT 通过 ROS/MAPK/MMP 信号轴发挥作用，减少组织退化并改善缺血性伤口愈合。
