Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1.
Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1.
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DOI：
10.1097/shk.0b013e31829f91fc
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Kozar RA
中科院分区：
文献类型：
--
作者：
Peng Z;Pati S;Potter D;Brown R;Holcomb JB;Grill R;Wataha K;Park PW;Xue H;Kozar RA
我们最近证实，失血性休克中受伤的患者会排出syndecan-1，并且这些患者早期使用新鲜冰冻血浆(FFP)与改善临床结果相关。由于肺在创伤后经常受到损伤，我们假设失血性休克诱导的syndecan-1脱落使肺血管内皮细胞暴露在损伤之下，导致炎症和高通透性，这些影响将被FFP缓解。在体外，用等量的FFP或乳酸林格氏(LR)孵育肺内皮细胞，测定肺内皮细胞通透性、内皮细胞单层通透性、跨内皮细胞电阻(TER)和白细胞与内皮的结合。在体内，采用创伤和失血性休克的凝血病态小鼠模型，观察1XFFP或3XLR复苏3小时后肺高通透性、中性粒细胞浸润、Syndecan-1表达和全身脱落，并与单纯休克和假手术进行比较。在体外，与LR处理的内皮细胞相比，FFP可降低内皮通透性和通透性，增加TER，并抑制白细胞与内皮的结合。在活体内，失血性休克与Syndecan-1的全身脱落有关，而Syndecan-1与肺SYDNECAN-1的降低以及肺血管高通透性和炎症的增加有关。与LR复苏相比，FFP复苏消除了这些损伤效应。失血性休克后，FFP复苏可抑制内皮细胞的高通透性和炎症反应，恢复肺组织Syndecan-1的表达。调节肺组织Syndecan-1的表达可能是FFP有益的机制之一。
We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan-1 and that the early use of fresh frozen plasma (FFP) in these patients is correlated with improved clinical outcomes. As the lungs are frequently injured after trauma, we hypothesized that hemorrhagic shock-induced shedding of syndecan-1 exposes the underlying pulmonary vascular endothelium to injury resulting in inflammation and hyperpermeability, and that these effects would be mitigated by FFP. In vitro, pulmonary endothelial permeability, endothelial monolayer flux, transendothelial electrical resistance (TER), and leukocyte-endothelial binding were measured in pulmonary endothelial cells after incubation with equal volumes of FFP or lactated Ringers (LR). In vivo, using a coagulopathic mouse model of trauma and hemorrhagic shock, pulmonary hyperpermeability, neutrophil infiltration, and syndecan-1 expression and systemic shedding were assessed after three hours of resuscitation with either 1XFFP or 3XLR and compared to shock alone and shams. In vitro, endothelial permeability and flux were decreased, TER was increased, and leukocyte-endothelial binding was inhibited by FFP compared to LR treated endothelial cells. In vivo, hemorrhagic shock was associated with systemic shedding of syndecan-1 which correlated with decreased pulmonary sydnecan-1 and increased pulmonary vascular hyperpermeability and inflammation. FFP resuscitation, compared to LR resuscitation, abrogated these injurious effects. After hemorrhagic shock, FFP resuscitation inhibits endothelial cell hyperpermeability and inflammation and restores pulmonary syndecan-1 expression. Modulation of pulmonary syndecan-1 expression may mechanistically contribute to the beneficial effects FFP.