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Abdominal surgery induced gastric ileus and activation of M1 like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats

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AJP Gastrointestinal and Liver Physiology

Published online on

Abstract

Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. The stable thyrotropin-releasing hormone agonist, RX77368 injected intracisternally (ic) activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by ic RX-77368 in rats. RX77368 (50 ng/rat) or saline was injected ic followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. Sham group had anesthesia alone. After 6-h, gastric emptying (GE) and the inflammation in gastric corpus were determined. AS inhibited GE by 72% vs control. In whole mount preparation of myenteric plexus, AS doubled the number of M1-like macrophage immunoreactive for MHCII (M1 marker) but not for CD206 (M2 marker) (MHCII+/CD206-) while there was no change in M2-like macrophages (MHCII-/CD206+). AS increased mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the gastric submucosa plus muscle layers by 1.7- and 1.5-fold respectively and the infiltration of neutrophils labeled by myeloperoxidase in the muscularis externa by 9.5-fold. RX77368 inhibited AS-related gastric changes while not altering these parameters in sham group. There was a significant negative correlation between GE and IL-1β (r=-0.46), TNF-α (r=-0.44), M1 macrophage (r=-0.82) and neutrophils (r=-0.91). The M2 like macrophages and IL-10 expression were unchanged after AS with ic saline or RX77368. These data indicate that AS activates gastric M1 macrophages and increases proinflammatory cytokines expression that are prevented by central vagal activation and may contribute to the correlated prevention of postoperative gastric ileus.