Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice.
Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice.
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DOI：
10.1097/shk.0000000000000452
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发表时间：
2015-11
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：
Ban K;Peng Z;Pati S;Witkov RB;Park PW;Kozar RA
我们已经在失血性休克（HS）的啮齿动物模型中显示，新鲜冷冻血浆（FFP）减少与多配体蛋白聚糖-1的恢复相关的肺部炎症和损伤。由于肠道被认为有助于休克后的远端器官损伤和炎症，目前的研究试图确定血浆的保护作用是否会延伸到肠道，并阐明syndecan-1对这种保护作用的贡献。我们还研究了TNFα和去整合素和金属蛋白酶（ADAM）-17的潜在作用，这两种酶都是syndecan-1的肠道脱落酶。野生型（WT）和syndecan-1−/−（KO）小鼠接受HS，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小时后取小肠和血液用于分析粘膜损伤和炎症以及TNFα和ADAM-17蛋白表达和活性。HS后，肠道损伤和炎症显着增加相比，假。LR复苏可减少损伤和炎症，FFP可进一步减轻损伤和炎症。与WT小鼠相比，KO小鼠在HS后显示出恶化的肠道损伤和炎症，LR和FFP同等地抑制损伤和炎症。全身和肠道TNFα和ADAM-17均遵循相似的趋势，在WT但非KO小鼠中，HS后升高，LR降低，FFP进一步降低。总之，FFP减少了失血性休克后的肠道损伤和炎症，这种作用在syndecan-1−/−小鼠中被消除。血浆中TNFα和ADAM-17也减少，这代表了通过syndecan-1保护的潜在机制。
We have shown in a rodent model of hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces lung inflammation and injury which are correlated with restitution of syndecan-1. Since the gut is believed to contribute to distant organ injury and inflammation after shock, the current study sought to determine if the protective effects of plasma would extend to the gut and to elucidate the contribution of syndecan-1 to this protective effect. We also examined the potential role of TNFα, and a disintegrin and metalloproteinase (ADAM)-17, both intestinal sheddases of syndecan-1. Wild-type (WT) and syndecan-1−/− (KO) mice were subjected to HS followed by resuscitation with lactated ringers (LR) or FFP and compared to shock alone and shams. Small bowel and blood were obtained after 3 hours for analysis of mucosal injury and inflammation and TNFα and ADAM-17 protein expression and activity. After HS, gut injury and inflammation were significantly increased compared to shams. Resuscitation with LR decreased both injury and inflammation which were further lessened by FFP. KO mice displayed worsened gut injury and inflammation after HS compared to WT mice, and LR and FFP equivalently inhibited injury and inflammation. Both systemic and intestinal TNFα and ADAM-17 followed similar trends, with increases after HS, reduction by LR, and a further decrease by FFP in WT but not KO mice. In conclusion, FFP decreased gut injury and inflammation after hemorrhagic shock, an effect that was abrogated in syndecan-1−/− mice. Plasma also decreased TNFα and ADAM-17, representing a potential mechanistic link to its protection via syndecan-1.