Ousaka Daiki, Nishibori Masahiro
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences.
Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences.
Nihon Yakurigaku Zasshi. 2022;157(6):422-425. doi: 10.1254/fpj.22073.
Sepsis is one of the leading cause of death worldwide. Recently, several studies suggested that free-hemoglobin and heme derived from hemolysis are important factors which may be associated with severity of septic patients including COVID-19. In other words, hemolysis-derived products enhance the inflammatory responses as damage-associated molecular patterns (DAMPs) in both intravascular and extravascular space. In addition, hemoglobin has vasoconstrictive activity by depleting nitric oxide, whereas heme or Fe produce reactive oxygen species (ROS) through Fenton reaction leading to tissue injury. At present, we have no therapeutic options against sepsis-related hemolysis in clinical settings, however, there might be two therapeutic strategies in this regard. One is supplemental therapy of depleted scavenging proteins such as haptoglobin and hemopexin, the other is activation of the internal scavenging system including macrophage-CD163 pathway. These novel targets against sepsis are also critical for the next pandemic. In this review, we summarize the current issues regarding sepsis-related hemolysis including COVID-19, as well as for future perspectives.
脓毒症是全球主要的死亡原因之一。最近，多项研究表明，溶血产生的游离血红蛋白和血红素是可能与包括新冠肺炎患者在内的脓毒症患者病情严重程度相关的重要因素。换句话说，溶血衍生产物作为损伤相关分子模式（DAMPs）在血管内和血管外空间增强炎症反应。此外，血红蛋白通过消耗一氧化氮具有血管收缩活性，而血红素或铁通过芬顿反应产生活性氧（ROS），导致组织损伤。目前，在临床环境中我们没有针对脓毒症相关溶血的治疗选择，然而，在这方面可能有两种治疗策略。一种是补充消耗的清除蛋白，如触珠蛋白和血红素结合蛋白，另一种是激活包括巨噬细胞-CD163途径在内的内源性清除系统。这些针对脓毒症的新靶点对下一次大流行也至关重要。在这篇综述中，我们总结了包括新冠肺炎在内的脓毒症相关溶血的当前问题以及未来展望。
