NEUTROPHIL ELASTASE INHIBITOR IMPROVES SURVIVAL OF RATS WITH CLINICALLY RELEVANT SEPSIS
NEUTROPHIL ELASTASE INHIBITOR IMPROVES SURVIVAL OF RATS WITH CLINICALLY RELEVANT SEPSIS
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DOI：
10.1097/shk.0b013e3181cc064b
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发表时间：
2010-05-01
期刊：
影响因子：
3.1
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
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作者：
Suda, Koichi;Takeuchi, Hiroya;Kitagawa, Yuko
西维来司钠是一种选择性中性粒细胞弹性蛋白酶抑制剂，对全身炎症反应综合征相关的急性肺损伤有效。然而，西维来司他在脓毒症中的有效性尚未得到充分研究。在本研究中，研究了西维来司对大鼠盲肠结扎穿孔（CLP）模型中严重脓毒症的影响。成年雄性Sprague-Dawley大鼠进行CLP，并随机分为两组：西维来司治疗组和生理盐水治疗对照组。测定几种炎症介质的血清浓度。对肺进行苏木精-伊红染色和高迁移率族蛋白1（HMGB 1）、IL-8和CD 68的免疫组织化学染色，以评估CLP手术后12 h发现的病理变化。西维来司治疗显著提高了CLP后脓毒症动物的存活率（P = 0.030）。西维来司他还诱导这些CLP大鼠血清IL-1 β（P = 0.038）和IL-10（P = 0.008）水平显著降低。西维来司治疗组与对照组血清HMGB 1水平无显著差异。西维来司治疗组大鼠肺组织病理改变较轻，HMGB 1、IL-8和CD 68阳性细胞数减少（P < 0.001）。西维来司显著提高了具有临床相关脓毒症的大鼠的存活率，这可能是通过减轻脓毒症诱导的全身炎症反应和肺损伤。这可能解释了西维来司他在降低脓毒症发病率和死亡率方面的相关健康益处。
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-1 beta (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.