Effect of Octreotide on Enteric Motor Neurons in Experimental Acute Necrotizing Pancreatitis

BACKGROUND/AIMS Amelioration of intestinal dysmotility and stasis during the early period of acute necrotizing pancreatitis (ANP) appears to be important to reduce the risks of secondary pancreatic infection. We aimed to characterize the association between the neuropathy of the enteric nervous system and gut dysfunction and to examine the effect of octreotide on motor innervation in the early stage of ANP. METHODOLOGY/PRINCIPAL FINDINGS The rats were randomly divided into eight groups: control+saline; control+octreotide; ANP+saline and ANP+octreotide (24 h, 48 h, 72 h). The spontaneous activity of ileal segments and the response to ACh, l-NNA were recorded. The alterations of myenteric neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), PGP9.5 and somatostatin receptor 2 (SSTR(2)) immunoreactive cells were evaluated by immunofluorescence and the protein expression of nNOS and CHAT were evaluated by western blot. We found the amplitude of spontaneous contractions at 48 h and the response to ACh at 24 h declined in the ANP+saline rats. A higher contractile response to both ACh and to l-NNA was observed in the ANP+octreotide group, compared with the ANP+saline rats at 24 h. A significant reduction in the nNOS and cholinergic neurons was observed in ANP+saline rats at the three time points. However, this reduction was greatly ameliorated in the presence of octreotide at 24 h and 48 h. The protein expression of CHAT neurons at 24 h and the nNOS neurons at 48 h in the ANP+octreotide rats was much higher than the ANP+saline rats. CONCLUSION The pathogenesis of ileus in the early stage of ANP may be related to the neuropathy of the enteric nervous system. Octreotide may reduce the severity of ileus by lessening the damage to enteric motor innervation.