Ethyl pyruvate reduces the development of zymosan-induced generalized inflammation in mice
Ethyl pyruvate reduces the development of zymosan-induced generalized inflammation in mice
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DOI：
10.1097/ccm.0b013e318192fa63
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发表时间：
2009-01-01
影响因子：
8.8
通讯作者：
Cuzzocrea, Salvatore
中科院分区：
文献类型：
--
作者：
Di Paola, Rosanna;Mazzon, Emanuela;Cuzzocrea, Salvatore
目的：丙酮酸乙酯（EP）是一种简单的脂肪族酯，在先前的许多细胞培养和动物研究中已显示具有抗炎作用。在本研究中，我们调查了EP（75 mg/kg IP）对由酵母聚糖引起的休克发展的影响。设计：前瞻性，随机研究。设置：基于大学的研究实验室。主题：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给予IP）或载体（0.25 mL/小鼠盐水）。在酵母聚糖施用后1和6小时施用EP（75 mg/kg IP）。在施用酵母聚糖和/或EP后18小时评估小鼠中的器官衰竭和全身炎症。测量和主要结果：用EP处理小鼠减弱了由酵母聚糖引起的腹膜渗出和多形细胞的迁移。EP还减轻酵母多糖引起的肺、肝、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的增加。诱导型一氧化氮合酶，硝基酪氨酸，聚（AD 13-核糖），肿瘤坏死因子-α，白细胞介素-1 β的免疫组织化学分析显示阳性染色的胰腺和肠组织从酵母多糖注射小鼠。染色硝基酪氨酸，诱导型一氧化氮合酶，聚（ADP-核糖），肿瘤坏死因子-a，和白细胞介素-1 β的程度显着减少，从酵母多糖注射小鼠，已收到EP的组织切片。此外，酵母聚糖的给药在小鼠中引起了严重的疾病，其特征在于全身毒性、体重显著减轻和观察期结束时（7天）60%的死亡率。治疗EP显着降低了全身毒性的发展，体重的损失，和死亡率（20%）所造成的zymosan.Conclusions：这项研究提供了证据，EP减弱酵母多糖诱导的休克小鼠的程度。(Crit Care Med 2009; 37：270 - 282）
Objective: Ethyl pyruvate (EP) is a simple aliphatic ester, which has been shown to have anti-inflammatory effects in previous numerous cell culture and animal studies. In the present study, we investigated the effects of EP (75 mg/kg IP) on the development of 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 IP as a suspension in saline) or vehicle (0.25 mL/mouse saline). EP (75 mg/kg IP was administered 1 and 6 hrs after zymosan administration. Organ failure and systemic inflammation in mice was assessed 18 hrs after administration of zymosan and/or EP.Measurements and Main Results: Treatment of mice with EP attenuated the peritonea[ exudation and the migration of polymorphonuclear cells caused by zymosan. EP also attenuated the lung, liver, and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase activity in the lung and intestine caused by zymosan. Immunohistochernical analysis for inducible nitric oxide synthase, nitrotyrosine, poly (AD13-ribose), tumor necrosis factor-a, and interleukin-1 beta revealed positive staining in pancreatic and intestinal tissue obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, inducible nitric oxide synthase, poly (ADP-ribose), tumor necrosis factor-a, and interleukin-1 beta were markedly reduced in tissue sections obtained from zymosan-injected mice, which had received EP. In addition, administration of zymosan caused a severe illness in the mice characterized by a systemic toxicity, significant loss of body weight, and a 60% of mortality at the end of observation period (7 days). Treatment with EP significantly reduced the development of systemic toxicity, the loss in body weight, and the mortality (20%) caused by zymosan.Conclusions: This study provides evidence that EP attenuates the degree of zymosan-induced shock in mice. (Crit Care Med 2009; 37:270 -282)