Changes of Intestinal Aquaporins after Experimental Polytrauma and Hemorrhagic Shock

Polytrauma (PT) and hemorrhagic shock (HS) can result in multiple organ dysfunction syndrome, with the intestine playing a critical role as a remote trauma organ due to disruption of the gut-blood barrier and associated fluid imbalances. At the molecular level, the role of both tight junction proteins, which maintain barrier sealing, and aquaporins (AQPs), which regulate water transport, remains not fully understood in the context of trauma.

We hypothesize that remote intestinal injury results in altered expression patterns of key AQPs (AQP1 and AQP3) and tight junction proteins in the small and large intestine following PT and HS.

A long-term porcine model of PT with or without HS was employed, incorporating guideline-driven intensive care management. Animals were assigned to three experimental groups and corresponding samples analyzed: Sham (n = 9), PT alone (n = 8), and PT with HS (n = 5). Inflammatory mediators, intestinal damage markers, and antimicrobial peptides were assessed in blood samples during the time course after trauma. At 72 hours after injury, ileum and colon tissues were harvested for gene expression analyses of tight junction molecules and AQPs (AQP1 and AQP3).

PT and HS caused a significant elevation in the antimicrobial peptides calprotectin and β-defensin. The analysis of tight junction protein expression revealed an unaffected intestinal expression profile of claudin-1 and occludin following experimental PT or PT + HS. In the colon, there was a significant reduction in the expression profile of tight junction protein-1 after PT, and a reduction in the expression of the sodium/bicarbonate cotransporter after both PT and PT + HS. In the ileum, there was a striking loss of 80% AQP1 expression in the PT and PT + HS group and a 54% decrease in AQP3 in the PT + HS group. However, these changes were not seen in the colon.

The PT and HS-driven reduction of key AQPs in the ileum may contribute to persistent gut-blood barrier dysfunction and could offer therapeutic targets to restore the intestinal fluid homeostasis following PT and HS.