Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia–Reperfusion Injury

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• 作者：Seisho Sakai (1)
  Hidehiro Tajima (1)
  Tomoharu Miyashita (1)
  Shin-ichi Nakanuma (1)
  Isamu Makino (1)
  Hironori Hayashi (1)
  Hisatoshi Nakagawara (1)
  Hirohisa Kitagawa (1)
  Sachio Fushida (1)
  Takashi Fujimura (1)
  Hidehito Saito (2)
  Seiichi Munesue (2)
  Yasuhiko Yamamoto (2)
  Tetsuo Ohta (1)
  
• 关键词：Ischemia–reperfusion injury ; Liver failure ; Neutrophil elastase inhibitor ; Sivelestat sodium hydrate ; Systemic inflammatory response syndrome
• 刊名：Digestive Diseases and Sciences
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：59
• 期：4
• 页码：787-794
• 全文大小：4,808 KB
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• 作者单位：Seisho Sakai (1)
  Hidehiro Tajima (1)
  Tomoharu Miyashita (1)
  Shin-ichi Nakanuma (1)
  Isamu Makino (1)
  Hironori Hayashi (1)
  Hisatoshi Nakagawara (1)
  Hirohisa Kitagawa (1)
  Sachio Fushida (1)
  Takashi Fujimura (1)
  Hidehito Saito (2)
  Seiichi Munesue (2)
  Yasuhiko Yamamoto (2)
  Tetsuo Ohta (1)
  
  1. Division of Cancer Medicine, Department of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
  2. Department of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
  
• ISSN：1573-2568

文摘

Background Sivelestat sodium hydrate (sivelestat) is a specific neutrophil elastase inhibitor that is effective in treating acute lung injury associated with systemic inflammatory response syndrome. As such, it may be useful in treating hepatic ischemia–reperfusion injury (IRI), a condition in which neutrophils transmigrate into the interstitium, leading to release of neutrophil elastase from neutrophils and consequent damage to the affected tissue, particularly in cases of hepatic failure after liver transplantation or massive liver resection. Aims The purpose of this study was to examine whether treatment with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and suppresses hepatic IRI. Methods Whether and, if so, the extent to which sivelestat suppresses the adhesion and migration of neutrophils and reduces liver damage in hepatic IRI was examined in a human umbilical vein endothelial cell (HUVEC) model and a rat hepatic IRI model. Results In the HUVEC model, the extent of the adhesion and migration of neutrophils stimulated by platelet-activating factor were found to be dose-dependently inhibited by sivelestat treatment (p?<?0.05). In the rat model, serum liver enzyme levels were significantly lower at 12?h after reperfusion, and the number of neutrophils that had migrated to extravascular sites was significantly less in the treatment group compared to the control group (p?<?0.05). Conclusion Sivelestat inhibits the adhesion and migration of neutrophils to vascular endothelium in hepatic IRI, thereby suppressing liver injury.