Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Biochem Pharmacol. 2022 May;199:115016. doi: 10.1016/j.bcp.2022.115016. Epub 2022 Mar 21.
Clinical incidences of pressure ulcers in the elderly and intractable skin ulcers in diabetic patients are increasing because of the aging population and an increase in the number of diabetic patients worldwide. Although various agents are used to treat pressure and skin ulcers, these ulcers are often refractory and deteriorate the patients' quality of life. Therefore, a novel therapeutic agent with a novel mechanism of action is required. Carbon monoxide (CO) contributes to many physiological and pathophysiological processes, including anti-inflammatory activity; therefore, it can be a therapeutic gaseous molecule. Recent studies have revealed that CO accelerates wound healing in gastrointestinal tract injuries. However, it remains unclear whether CO promotes cutaneous wound healing. Therefore, we aimed to evaluate the therapeutic effects of topical application of a CO-containing solution and elucidate the underlying mechanism. A full-thickness skin wound generated on the back of diabetic mice was treated topically with CO or vehicle. Sustained release of CO was achieved using polyacrylic acid (PAA) as a thickener. The administration of CO-containing PAA aqueous solution resulted in a significant acceleration in wound recovery without elevating serum CO levels in association with increased angiogenesis and supported by elevated expression of vascular endothelial growth factor mRNA in the wound granulomatous tissues. These data suggest that CO might represent a novel therapeutic agent for the treatment of cutaneous wounds.
由于人口老龄化和全球糖尿病患者数量的增加，老年人的压疮和糖尿病患者的难治性皮肤溃疡的临床发病率正在增加。尽管有各种药物用于治疗压疮和皮肤溃疡，但这些溃疡常常难以治愈，降低了患者的生活质量。因此，需要一种具有新作用机制的新型治疗剂。一氧化碳（CO）参与许多生理和病理生理过程，包括抗炎活性；因此，它可以成为一种治疗性气体分子。最近的研究表明，CO 可加速胃肠道损伤的伤口愈合。然而，CO 是否促进皮肤伤口愈合仍不清楚。因此，我们旨在评估局部应用含 CO 溶液的治疗效果，并阐明其潜在机制。在糖尿病小鼠的背部制造全层皮肤伤口，并用 CO 或载体局部处理。通过使用聚丙烯酸（PAA）作为增稠剂来实现 CO 的持续释放。含有 CO 的 PAA 水溶液的给药导致伤口恢复明显加速，而不会导致血清 CO 水平升高，这与血管生成增加有关，并伴有伤口肉芽组织中血管内皮生长因子 mRNA 的表达升高。这些数据表明，CO 可能代表一种治疗皮肤伤口的新型治疗剂。
