Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis
Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis
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DOI：
10.1097/01.ccm.0000275273.56547.b8
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发表时间：
2007-08-01
影响因子：
8.8
通讯作者：
Hsu, Su-Ming
中科院分区：
文献类型：
--
作者：
Tsao, Po-Nien;Chan, Feng-Tsan;Hsu, Su-Ming
目的：确定可溶性Flt-1（sFlt）（一种有效的血管内皮生长因子拮抗剂）在实验性内毒素血症和脓毒症中调节炎症的假定作用。设计：随机前瞻性实验研究。设置：大学医学实验室。受试者：雄性C56 BU/6品系小鼠。干预措施：我们研究了血管内皮生长因子和可溶性Flt-1在实验性内毒素休克和脓毒症中的表达模式和作用。可溶性Flt-1的可能的抗炎机制也进行了评估。测量和主要结果。血管内皮生长因子和sFlt-1在脂多糖体外激活的巨噬细胞和内毒素血症小鼠的血浆中迅速释放。在内毒素血症小鼠中，给予血管内皮生长因子可增强促炎性细胞因子的产生并介导死亡率的显著增加。治疗sFlt-1减弱炎症反应，抑制招募炎症细胞进入腹腔，并改善生存在一个致命的内毒素血症和盲肠结扎和穿刺诱导的脓毒症模型，甚至当给药迟至24小时后的发病sepsis.Conclusions：这些研究结果支持sFlt-1在内毒素休克和脓毒症的关键保护作用。因此，sFlt-1可能具有作为治疗脓毒症综合征的预防剂的效用。
Objective: To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis.Design: Randomized prospective experimental study.Setting: University medical laboratory.Subjects: Male C56BU/6 strain mice.Interventions: We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated.Measurements and Main Results. Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflarnmatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis.Conclusions: These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.