We have shown in a rodent model of
hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces
lung inflammation and injury that are correlated with restitution of
syndecan-1. As 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 Ringer's (LR) or FFP and compared with
shock alone and shams. Small bowel and blood were obtained after 3 h 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 with shams.
Resuscitation with LR decreased both injury and
inflammation that were further lessened by FFP. KO mice displayed worsened gut injury and
inflammation after HS compared with 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.