Erythropoietin reduces the development of nonseptic shock induced by zymosan in mice
Erythropoietin reduces the development of nonseptic shock induced by zymosan in mice
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DOI：
10.1097/01.ccm.0000207346.56477.e8
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发表时间：
2006-04-01
影响因子：
8.8
通讯作者：
Thiemermann, C
中科院分区：
文献类型：
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作者：
Cuzzocrea, S;Di Paola, R;Thiemermann, C
Objective.促红细胞生成素是红系祖细胞的有效刺激物，并且其表达被缺氧增强。在本研究中，我们研究了促红细胞生成素（1000 IU/kg皮下注射）对酵母多糖引起的非感染性休克发展的影响。前瞻性、随机研究。设置：基于大学的研究实验室。受试者：雄性CD小鼠。干预：小鼠接受腹膜内酵母聚糖（500 mg/kg，作为盐水中的悬浮液腹膜内施用）或载体（0.25 mL/小鼠盐水）。在酵母聚糖给药后1和6小时，以1000 IU/kg的剂量皮下给予促红细胞生成素。在施用酵母聚糖和/或促红细胞生成素后18小时评估小鼠中的器官衰竭和全身炎症。用促红细胞生成素（1000 IU/kg皮下注射，酵母多糖给药后1和6小时）处理小鼠，可减弱酵母多糖引起的腹膜渗出和多形核细胞迁移。促红细胞生成素还减弱酵母多糖引起的肺、肝和胰腺损伤和肾功能障碍，以及酵母多糖引起的肺和肠中髓过氧化物酶活性增加。硝基酪氨酸和聚（ADP-核糖）的免疫组织化学分析显示阳性染色的肺和肠组织从酵母多糖治疗的小鼠。硝基酪氨酸和聚（ADP-核糖）的染色程度显着减少，从酵母多糖治疗的小鼠，其中收到促红细胞生成素的组织切片。此外，酵母聚糖的给药在小鼠中引起严重疾病，其特征在于全身毒性、体重显著减轻和在观察期结束时70%的死亡率。治疗与促红细胞生成素显着降低了全身毒性的发展，体重的损失，和zymosan.Conclusions引起的死亡率：这项研究提供了证据，第一次，促红细胞生成素减弱的程度zymosan诱导的非感染性休克小鼠。
Objective. Erythropoietin is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. In the present study, we investigated the effects of erythropoietin (1000 IU/kg subcutaneously) on the development of nonseptic shock caused by zymosan.Design. Prospective, randomized study.Setting: University-based research laboratory.Subjects: Male CD mice.Interventions: Mice received either intraperitoneally zymosan (500 mg/kg, administered intraperitoneally as a suspension in saline) or vehicle (0.25 mL/mouse saline). Erythropoietin was administered at the dose of 1000 IU/kg subcutaneously, 1 and 6 hrs after zymosan administration. Organ failure and systemic inflammation in mice was assessed 18 hrs after administration of zymosan and/or erythropoietin.Measurements and Main Results., Treatment of mice with erythropoietin (1000 IU/kg subcutaneously, 1 and 6 hrs after zymosan administration) attenuated the peritoneal exudation and the migraton of polymorphonuclear cells caused by zymosan. Erythropoietin also attenuated the lung, liver, and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase activity caused by zymosan in the lung and intestine. Immunohistochemical analysis for nitrotyrosine and poly(ADP-ribose) revealed positive staining in lung and intestine tissues obtained from zymosan-treated mice. The degree of staining for nitrotyrosine and poly(ADP-ribose) was markedly reduced in tissue sections obtained from zymosan-treated mice, which received erythropoietin. In addition, administration of zymosan caused severe illness in the mice characterized by a systemic toxicity, significant loss of body weight, and a 70% mortality rate at the end of observation period Q days). Treatment with erythropoietin significantly reduced the development of systemic toxicity, the loss in body weight, and the mortality caused by zymosan.Conclusions: This study provides evidence, for the first time, that erythropoietin attenuates the degree of zymosan-induced nonseptic shock in mice.