INSERM, U694, Université d'Angers, Angers, France.
Crit Care Med. 2011 Jul;39(7):1739-48. doi: 10.1097/CCM.0b013e3182190b4b.
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.
Prospective, controlled experiments.
Animal basic science laboratory.
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.
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.
In heart and lungs, microparticles from septic shock patients increased the expression of endothelial and inducible nitric oxide synthases, cyclooxygenase-2, and nuclear factor-κB. 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 IκBα phosphorylation were decreased. Septic microparticles did not change superoxide anion and nitric oxide productions in kidneys.
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.
感染微生物后出现低血压和多器官衰竭的即为感染性休克。感染性休克患者的循环中存在高水平的微颗粒。这些微颗粒是由激活或凋亡细胞的质膜释放的小囊泡。在此，我们研究了来自非感染性或感染性患者的微颗粒在体内注射对小鼠组织中蛋白质表达的影响。
前瞻性、对照实验。
动物基础科学实验室。
雄性瑞士小鼠被随机分为两组：11 只注射来自健康供体的微颗粒，15 只注射来自感染性休克患者的微颗粒。
从感染性和非感染性患者的全血中提取微颗粒，并静脉注射到小鼠体内。24 小时后，处死小鼠，分离心脏、肺、肝和肾进行 Western blot 分析。还直接测量电子顺磁共振法测量器官中一氧化氮和超氧阴离子的产生。
在心脏和肺部，来自感染性休克患者的微颗粒增加了内皮型和诱导型一氧化氮合酶、环氧化酶-2 和核因子-κB 的表达。然而，只有心脏中增加了细胞外超氧化物歧化酶。这些作用与心脏和肺部的氧化或硝化应激增加有关，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，环氧化酶-2 表达和 IκBα 磷酸化减少。感染性休克的微颗粒未改变肾脏中超氧阴离子和一氧化氮的产生。
结果表明，来自感染性休克患者的微颗粒根据靶组织的不同，对与硝化和氧化应激相关的促炎蛋白的表达产生多效性和差异作用。因此，微颗粒可能参与感染性休克患者观察到的器官功能障碍。
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