Protective Effect Of Cholinergic Anti-inflammatory Pathway On Acute Esophagitis In Rats

AIM: To investigate the neural and pharmacal effects on the degree of esophagitis ,levels of cytokines,choline acetyltransferase(ChAT)and nitric oxide synthetase(NOS) activities and expressions of nitric oxide synthase (NOS) and c-Fos in medulla oblongata after esophageal acid-pepsin exposure.To determine the contribution of cholinergic anti-inflammatory pathway to acute esophagitis in rats.METHODS: Protocol I: Esophagitis was induced by perfusion of 0.1mol/L hydrochloric acid with pepsin in the lower part of the esophagus. Forty SD rats were divided into five groups. Group 1 served as a saline-treated control, while in group 2 the distal esophagus was exposed to acidified pepsin for 2h.In the other three groups, animals were subjected to sham surgery or bilateral cervical vagotomy alone or with electrical stimulation before and after acid perfusion. The levels of tumor necrosis factor-a (TNF- a ),interleukin-6(IL-6),interleukin-10(IL-10) and activities of ChAT and NOS were determined.Esophageal injury was accessed by macroscopic and microscopic examination. Protocolâ…¡:Forty SD rats were divided into five groups.In group 1,normal saline was perfused in the lower part of the esophagus.In group 2 to 4,saline,L-Arginine, sodium nitroprusside and L-NAME were injected before esophageal acid-pepsin perfusion. The severity of esophagitis and levels of cytokines, nitrite/nitrate were determined. NADPH-d histochemistry and c-Fos immunohistochemistry were respectively processed to observe the distribution of c-fos and NADPH-d neurons in medulla and the c-Fos and NADPH-d positive neurons were counted.RESULTS: (1)Esophageal perfusion with acidified pepsin induced acute mucosal damage.(2)The levels of TNF- a,IL-6,IL-10 and activities of ChAT and NOS in esophageal tissue increased after acid perfusion.Vagus nerve electrical stimulation inhibited the release of TNF- a, IL-6 and the degree of esophagitis, while amounts of the anti-inflammatory cytokine IL-10 were not affected. Conversely,vagotomy resulted in an enhanced severity of esophagitis, associated with significant increase of TNF - a and IL-6 levels and decrease of NOS activitiy.(3)c-Fos immunoreactivity was significantly increased in the nucleus tractus solitarius and dorsal motor nucleus of vagus (NTS&DMV), area postrema (AP),reticular nucleus of medulla (RNM) and nucleus ambiguous (NA) and NADPH-d reactivity increased in the NTS&DMV, RNM and NA following acid perfusion.(4)Compared to saline-treatment, in L-Arginine pretreatment group c-Fos immunoreactive cells of were markly higher in NTS&DMV, RFM and AP.So did SNP pretreatment in NTS&DMV and AP. L-NAME reduced c-Fos and NADPH-d reactivity in all the nuclei mentioned above.(5)The esophageal concentrations of TNF- a and IL-6 significantly decreased in the L-Arginine and SNP pretreatment groups,while IL-10 level did not changed.L-NAME pretreatment elevated IL-10 concentration and had no inference on that of TNF- a and IL-6.CONCLUSION: The results of this study provide evidence for the involvement of the cholinergic anti-inflammatory pathway in modulating inflammation and injury during experimental esophagitis. NO is likely one of the modulators of the cholinergic anti-inflammatory pathway.