Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.
Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.
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DOI：
10.1097/shk.0000000000000832
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Kozar RA
中科院分区：
文献类型：
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作者：
Wu F;Peng Z;Park PW;Kozar RA
Syndecan-1被认为是失血性休克后内皮糖萼损伤的生物标志物，sdc 1的脱落是有害的。用新鲜冷冻血浆（FFP）复苏与肺sdc 1的恢复和肺损伤的减少相关，但sdc 1对FFP在肺中的保护的精确贡献仍不清楚。使用人肺内皮细胞来评估FFP对sdc 1表达的时间和剂量依赖性作用以及sdc 1沉默对体外内皮细胞通透性和肌动蛋白应力纤维形成的作用。野生型（WT）和syndecan-1−/−小鼠经历失血性休克，然后用乳酸林格氏液（LR）或FFP复苏，并与单独休克和假手术进行比较。3小时后收获肺用于分析渗透性、组织学和炎症，并用于测量多配体蛋白聚糖-2和4表达。在体外，FFP增强肺内皮细胞sdc 1表达的时间和剂量依赖性的方式和sdc 1在肺内皮细胞的损失恶化的通透性和应力纤维形成的FFP。sdc 1在体内的丢失导致LR和FFP在恢复休克后的肺损伤、炎症和通透性方面的等效性。最后，sdc 1 −/−小鼠在失血性休克和基于FFP的复苏后肺syndecan 4表达显著增加。综上所述，我们的研究结果支持sdc 1在失血性休克后FFP调节肺保护中的关键作用。我们的研究结果还表明，syndecan家族的其他成员可能至少有助于FFP对内皮细胞的影响，这一领域值得进一步研究。
Syndecan-1 is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary sdc1 and reduction of lung injury, but the precise contribution of sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose dependent effect of FFP on sdc1 expression and the effect of sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type (WT) and syndecan-1−/− mice were subjected to hemorrhagic shock followed by resuscitation with lactated ringers (LR) or FFP and compared to shock alone and shams. Lungs were harvested after 3 hours for analysis of permeability, histology, and inflammation and for measurement of syndecan- 2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial sdc1 expression in time- and dose-dependent manners and loss of sdc1 in pulmonary endothelial cells worsened permeability and stress fiber formation by FFP. Loss of sdc1 in vivo lead to equivalency between LR and FFP in restoring pulmonary injury, inflammation, and permeability after shock. Lastly, sdc1 −/− mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFP based resuscitation. Taken together, our findings support a key role for sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP’s effects on the endothelium, an area that warrants further investigation.