Neutrophil Elastase Inhibition Ameliorates Endotoxin-induced Myocardial Injury Accompanying Degradation of Cardiac Capillary Glycocalyx
| Autor: | Saori Matsuo, Akihiro Uchida, Chihiro Takada, Ayane Nishio, Shinji Ogura, Hiroaki Ushikoshi, Hirotsugu Fukuda, Genzou Takemura, Hiroyuki Tomita, Ayumi Kuroda, Tomoaki Doi, Ryogen Zaikokuji, Kazumasa Oda, Isamu Muraki, Yoichi Maekawa, Kodai Suzuki, Takahiro Yoshida, So Sampei, Yasuaki Hotta, Kentaro Morishita, Tetsuya Fukuta, Akio Suzuki, Hirohisa Yano, Takatomo Watanabe, Hideshi Okada, Nagisa Miyazaki, Noriaki Yamada, Shozo Yoshida |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Glycine Pharmacology Glycocalyx Critical Care and Intensive Care Medicine Sepsis Mice medicine Animals Mice Knockout Sulfonamides biology Interleukin-6 business.industry Troponin I Granulocyte-Macrophage Colony-Stimulating Factor Basic Science Aspects medicine.disease Endotoxemia Endotoxins Microscopy Electron Neutrophil elastase Emergency Medicine biology.protein Erratum Leukocyte Elastase business |
| Zdroj: | Shock |
| Popis: | Myocardial injury in sepsis may be caused by a burst of several inflammatory mediators, leading to vascular endothelial injuries. However, the contribution of neutrophil elastase (NE) to myocardial injury in sepsis is still unknown. We aimed to evaluate whether endotoxemia-induced myocardial injury is associated with NE. Lipopolysaccharide (LPS) was injected intraperitoneally at a dose of 20 mg/kg into granulocyte-colony-stimulating-factor knockout mice (G-CSF-KO), which have few neutrophils, and littermate control mice. The survival rate of G-CSF-KO mice 48 hours after LPS injection was significantly greater than that of control mice. The serum level of troponin I in G-CSF-KO mice was significantly lower than that in control mice. In addition, the concentration of inflammatory cytokine interleukin-6 (IL-6) was significantly decreased 6 and 12 hours after LPS administration compared with that in control mice. Ultrastructural analysis revealed that vascular endothelial structures and the endothelial glycocalyx in G-CSF-KO mice were clearly preserved. Next, mice were injected with 0.2 mg/kg sivelestat (an NE inhibitor) after LPS administration. The survival rate was significantly higher and the serum level of troponin I was lower in sivelestat-injected mice than in control mice, respectively. Furthermore, IL-6 levels were significantly decreased 6 and 12 hours after LPS administration compared with those in control mice. Vascular endothelial structures and the endothelial glycocalyx in sivelestat-treated mice were clearly preserved at the ultrastructural level. In conclusion, NE is significantly associated with myocardial injury in endotoxemia. Inhibition of NE may be a useful tool for the management of endotoxemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|