MALT Lymphoma, Stress Ulcer and Cholinergic Nerves from the Viewpoint of Bilateral and Unilateral Truncal Vagotomy and Substance P

Abstract

Background: Vagal nerve plays an important role in the stomach function. The cholinergic nerves are the most abundantly distributed nerves in the gastric tissue. It has recently been reported that the vagal nerve is significantly related to both gastric cancer development and progression. However, its relation to the mesenchymal tumor, including MALT lymphoma, is not known. In this study, we investigated the effect of unilateral truncal vagotomy on gastric MALT lymphoma development by using Helicobacter heilmannii-infected mouse model as well as that of bilateral truncal vagotomy on stress-induced ulcer formation. Methods: In the first part of this study, the distribution of the cholinergic nerves in the rat gastric mucosa and the effect of bilateral truncal vagotomy, as well as various kinds of agents acting on autonomic nerves in rats, were investigated by the histochemical and macroscopic method. In the second part, we employed MALT lymphoma formation in C57BL/6NCrl mice that were infected with Helicobacter heilmannii. A total of 38 infected mice underwent unilateral vagotomy under microscopy. The mice were randomized into 4 groups from which samples were collected; 2, 3, 4 and 6 months after infection. Both the anterior and posterior sides of the stomachs were sampled from each mouse for pathological and immunohistochemical analyses. Results: The bilateral truncal vagotomy significantly suppressed the restraint-induced gastric ulcer formation in rats, while bethanechol, and 6-hydroxydopamine led to an increase of the gastric ulcer formation. In the unilateral truncal vagotomy study using MALT lymphoma, the thickness of the gastric mucosa was reduced in the vagotomized side compared to the non-vagotomized side. Furthermore, the gastric MALT lymphoma was more prominently found in the vagotomized anterior side of stomach compared with that in the non-vagotomized posterior side of stomach. Substance P-immunoreactive nerves markedly increased surrounding the MALT lymphoma and the neurokinin-1 receptor immunoreactive lymphocytes increased within the MALT lymphoma in the vagotomized side. In conclusion, vagotomy enhanced gastric MALT lymphoma development possibly through the substance P-neurokinin-1 receptor pathway.