Relationship between disruption of the unstirred mucus layer and intestinal restitution in loss of gut barrier function after trauma hemorrhagic shock

Abstract

The factors involved in shock-induced loss of gut barrier function remain to be defined fully and studies investigating gut injury have focused primarily on the systemic side of the intestine. Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of trauma sham shock (T/SS) or actual trauma (laparotomy) hemorrhagic shock (T/HS) (30 mm Hg). At 0, 30, 60, or 180 minutes after the end of shock and volume resuscitation (reperfusion), the animals were killed and samples of the ileum were collected for intestinal morphologic analysis, analysis of the unstirred mucus layer, and for barrier function by measuring permeability to flourescein dextran. T/HS-induced morphologic evidence of mucosal injury as well as epithelial apoptosis was present at the end of the shock period and maximal after 60 minutes of reperfusion. At 3 hours after reperfusion, the degree of villous injury and enterocyte apoptosis had decreased. In contrast to the morphologic appearance of the villi, disruption of the mucus layer became progressively more severe over time and was manifest as a decrease in mucus thickness, progressive loss of coverage of the luminal surface by the mucus layer, and a change in mucus appearance from a dense to a loose structure. Studies of intestinal permeability documented that T/HS-induced loss of gut barrier function persisted throughout the 3-hour reperfusion period and were associated with injury to the mucus layer as well as the villi. T/HS leads to changes in the intestinal mucus layer as well as increased villous injury, apoptosis, and gut permeability. Additionally, increased gut permeability was associated with loss of the intestinal mucus layer suggesting that T/HS-induced injury to the mucus layer may contribute to the loss of gut barrier function.