Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress
Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress
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DOI：
10.1097/ccm.0b013e3182190b4b
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发表时间：
2011-07-01
影响因子：
8.8
通讯作者：
Andriantsitohaina, Ramaroson
中科院分区：
文献类型：
--
作者：
Mastronardi, Maria Letizia;Mostefai, Hadj Ahmed;Andriantsitohaina, Ramaroson
目的：感染性休克是由微生物感染引起的以低血压和多器官功能衰竭为特征的疾病。感染性休克患者显示高水平的循环微粒。这些是从活化或凋亡细胞的质膜释放的小泡。在这里，我们研究了体内注射来自非脓毒症或脓毒症受试者的微粒对小鼠组织中蛋白质表达的影响。设计：前瞻性对照实验。设置：动物基础科学实验室。受试者：雄性瑞士小鼠被随机分配到两组之一：11只动物注射从健康受试者分离的微粒，15只动物注射从败血症受试者分离的微粒。干预：从脓毒症和非脓毒症受试者的全血中提取微粒，并静脉注射到小鼠中。24小时后，杀死小鼠，分离心脏、肺、肝脏和肾脏用于蛋白质印迹分析。器官也被用于直接测量一氧化氮和超氧阴离子的生产通过电子顺磁resonance. Measures和主要结果：在心脏和肺，微粒从感染性休克患者增加内皮细胞和诱导型一氧化氮合酶，环氧合酶-2，和核因子-κ B的表达。然而，细胞外超氧化物歧化酶仅在心脏中增加。这些影响与心脏和肺中更大的氧化或硝化应激有关，而不影响一氧化氮的产生。肝脏表现出与内皮型一氧化氮合酶和锰超氧化物歧化酶表达降低相关的氧化应激增加。然而，环氧合酶-2表达和I κ B α磷酸化降低。脓毒症微粒没有改变超氧阴离子和一氧化氮productioninkidney.Conclusions：结果表明，从脓毒症休克患者的微粒发挥多效性和差异的影响，这取决于靶组织方面的促炎蛋白的表达与硝化和氧化应激。因此，微粒可能参与在感染性休克患者中观察到的器官功能障碍。(Crit Care Med 2011; 39：1739-1748）
Objective: Septic shock is characterized by hypotension and multiple organ failure after infection of microorganisms. Septic shock patients display high levels of circulating microparticles. These are small vesicles released from the plasma membrane of activated or apoptotic cells. Here, we have investigated the effects of in vivo injection of microparticles from nonseptic or septic subjects on protein expression in mouse tissues.Design: Prospective, controlled experiments.Setting: Animal basic science laboratory.Subjects: Male Swiss mice were randomly assigned to one of two groups: 11 animals injected with microparticles isolated from healthy subjects and 15 animals injected with microparticles isolated from septic patients.Interventions: Microparticles were extracted from whole blood of septic and nonseptic subjects and were intravenously injected in mice. After 24 hrs, mice were killed and heart, lungs, liver, and kidneys were isolated for Western blot assays. Organs were also used for direct measurements of nitric oxide and superoxide anion production by electron paramagnetic resonance.Measurements and Main Results: In heart and lungs, microparticles from septic shock patients increased the expression of endothelial and inducible nitric oxide synthases, cyclooxygenase-2, and nuclear factor-kappa B. However, extracellular superoxide dismutase was only increased in the heart. These effects were associated either with a greater oxidative or nitrative stress in heart and lungs, without affecting nitric oxide production. The liver exhibited an increase in oxidative stress linked to decreased endothelial nitric oxide synthase and manganese superoxide dismutase expression. However, cyclooxygenase-2 expression and I kappa B alpha phosphorylation were decreased. Septic microparticles did not change superoxide anion and nitric oxide productions in kidneys.Conclusions: Results suggest that microparticles from septic shock patients exert pleiotropic and differential effects depending on target tissues with regard to the expression of proinflammatory proteins related with nitrative and oxidative stresses. Thus, microparticles might participate in organ dysfunction observed in septic shock patients. (Crit Care Med 2011; 39: 1739-1748)