Department of Surgery, School of Medicine, Keio University, Shinanomachi 35, Shinjuku-ku, Tokyo, Japan.
Shock. 2010 May;33(5):526-31. doi: 10.1097/SHK.0b013e3181cc064b.
Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase, which is effective in acute lung injury associated with systemic inflammatory response syndrome. However, the effectiveness of sivelestat in sepsis has not been fully examined. In the present study, the effect of sivelestat on severe sepsis in a rat cecal ligation and puncture (CLP) model was investigated. Adult male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: sivelestat-treated group and saline-treated controls. The serum concentrations of several inflammatory mediators were measured. Hematoxylin-eosin staining, and immunohistochemical staining for high-mobility group box chromosomal protein 1 (HMGB1), IL-8, and CD68 were performed on the lungs to assess pathological changes found 12 h after the CLP procedure. Treatment with sivelestat significantly improved the survival rate of the post-CLP septic animals (P = 0.030). Sivelestat also induced a significant reduction in serum IL-1beta (P = 0.038) and IL-10 (P = 0.008) levels in these CLP rats. Serum HMGB1 levels had no significant difference between the sivelestat-treated and the control group. The lungs from sivelestat-treated rats exhibited less severe pathological changes and decreased the numbers of HMGB1, IL-8, and CD68-positive cells (P < 0.001). Sivelestat significantly improved survival rate of rats with clinically relevant sepsis, possibly by attenuating sepsis-induced systemic inflammatory response and lung injury. This may explain the implicated health benefits of sivelestat in reducing morbidity and mortality from sepsis.
盐酸西维来司他钠是中性粒细胞弹性蛋白酶的选择性抑制剂，在全身炎症反应综合征相关的急性肺损伤中具有疗效。然而，西维来司他钠在脓毒症中的疗效尚未得到充分研究。本研究旨在探讨盐酸西维来司他钠对盲肠结扎穿孔（CLP）模型大鼠严重脓毒症的作用。成年雄性 Sprague-Dawley 大鼠行 CLP 术，并随机分为西维来司他钠治疗组和生理盐水对照组。检测两组大鼠血清中几种炎症介质的浓度，观察术后 12 h 肺组织的病理变化，并行苏木精-伊红（H&E）染色、高迁移率族蛋白 1（HMGB1）、白细胞介素-8（IL-8）和 CD68 免疫组化染色。西维来司他钠治疗可显著提高 CLP 后脓毒症大鼠的生存率（P = 0.030），并降低血清中白细胞介素-1β（P = 0.038）和白细胞介素-10（P = 0.008）的水平。两组大鼠血清 HMGB1 水平无显著差异。与对照组相比，西维来司他钠治疗组大鼠的肺组织病理变化较轻，HMGB1、IL-8 和 CD68 阳性细胞数减少（P < 0.001）。盐酸西维来司他钠可提高临床相关脓毒症大鼠的生存率，可能是通过减轻脓毒症引起的全身炎症反应和肺损伤。这可能解释了西维来司他钠在降低脓毒症发病率和死亡率方面的潜在健康益处。
