Miyauchi Hiroaki, Okubo Koshu, Iida Kiriko, Kawakami Hiroshi, Takayama Kentaro, Hayashi Yoshio, Haruta Junji, Sasaki Junichi, Hayashi Kaori, Hirahashi Junichi
Department of General Medicine Education, School of Medicine, Keio University, Tokyo, Japan.
Department of Endocrinology, Metabolism and Nephrology, School of Medicine, Keio University, Tokyo, Japan.
Front Pharmacol. 2024 Aug 30;15:1458997. doi: 10.3389/fphar.2024.1458997. eCollection 2024.
Crush syndrome, which frequently occurs in earthquake disasters, often leads to rhabdomyolysis induced acute kidney injury (RIAKI). Recent findings indicate that systemic inflammatory response syndrome (SIRS) exacerbates muscle collapse, contributing to RIAKI. The purpose of this study is to investigate the involvement of multiple site inflammation, including intraperitoneal, in crush syndrome. In a mouse model of RIAKI, elevated levels of inflammatory mediators such as TNFα, IL-6, myoglobin, and dsDNA were observed in serum and the peritoneal cavity, peaking earlier in the intraperitoneal cavity than in serum or urine. Our previously developed novel peptide inhibiting leukocyte extracellular traps was administered intraperitoneally and blocked all of these mediators in the intraperitoneal cavity and serum, ameliorating muscle damage and consequent RIAKI. Although further studies are needed to determine whether intraperitoneal inflammation associated with muscle collapse can lead to systemic inflammation, resulting in more severe and prolonged muscle damage and renal injury, early suppression of multiple site inflammation, including intraperitoneal, might be an effective therapeutic target.
挤压综合征常发生于地震灾害中，常导致横纹肌溶解诱发的急性肾损伤（RIAKI）。最近的研究结果表明，全身炎症反应综合征（SIRS）会加剧肌肉损伤，进而导致RIAKI。本研究的目的是探讨包括腹腔内炎症在内的多部位炎症在挤压综合征中的作用。在RIAKI小鼠模型中，血清和腹腔内观察到炎症介质如TNFα、IL-6、肌红蛋白和双链DNA水平升高，腹腔内峰值出现时间早于血清或尿液。我们先前开发的新型抑制白细胞胞外陷阱的肽经腹腔注射，可阻断腹腔和血清中的所有这些介质，改善肌肉损伤及随之而来的RIAKI。尽管需要进一步研究来确定与肌肉损伤相关的腹腔内炎症是否会导致全身炎症，从而导致更严重、更持久的肌肉损伤和肾损伤，但早期抑制包括腹腔内炎症在内的多部位炎症可能是一个有效的治疗靶点。
