Abstract: Objective To observe the effect of intracerebroventricular (ICV) injection of nesfatin-1 on gastric acid secretion in rats, meanwhile its possible mechanism is also been investigated. Methods Male Sprague-Dawley rats were selected, and after ICV cannula implanted， the rats were randomly divided into control group and nesfatin-1 group, and the nesfatin-1 group was injected intracerebroventricularly with different concentrations(1、5 and 50pmol/rat) of nesfatin-1, control group was treated with the same amount of distilled water (5μl/rat). Optimum concentration of nesfatin-1 is used for the next subjects, then rats were sacrificed at different time points (20min,1,2,4 and 6h). The acid content of gastric juice were detected as before. The expression of histidine decarboxylase (HDC) mRNA and protein was examined by real-time PCR and Western blot. The changes in histamine in the gastric mucosa was detected by ELISA. Results ICV administration of nesfatin-1 significantly inhibited gastric acid output, the maximum inhibitory effect on gastric acid output was detected at the dose of 50 pmol/rat, and the optimum time for the gastric acid inhibition occured at 2 hours after ICV administration of nesfatin-1. Furthermore, nesfatin-1 decreased histidine decarboxylase (HDC) messenger RNA (mRNA) and protein expression levels in gastric mucosal tissue compaired to the control group .. Conclusions Our results suggest that nesfatin-1 dose and time dependently inhibited gastric acid secretion by ICV injection in rat, the histamine signaling may involve in this process.

Key words: Nesfatin-1, Gastric acid secretion, Histamine, Intracerebroventricular injection