Abstract: ABSTRACT Objective: To explore the changes and mechanismof gastriointestinal motility in the rats with chronic pancreatitis and the intervention effect of trimebutine maleate. Methods: Thirty wistar rats were divided into control,model and trimebutine maleate group randomly(n=10). Rats in model group were used to induce chronic pancreatitis by injecting oleic acid into the pancreatic duct. The control and model groups, administered intragastrically with physiological saline everyday. the Trimebutine Maleate group, administered intragastrically with Trimebutine Maleate everyday. The experiment period of each group are twe weeks. Eight weeks later, bowel movement coefficient and serum cholecystokinin(CCK) were detected, contractility of gastrointestinal circular muscle stripe and the contractile response of dispersed gastrointestinal circular smooth muscle cells stimulated by Aceylcholine (Ach) were measured. RT-PCR was used to detect the expression of inducible nitric oxide synthase (iNOS), mRNA within gastrointestinal muscularis , the level of nitric oxide (NO) in cell cultures was quantified. Results: The bowel movement coefficient, gastrointestinal circular smooth muscle stripes contractility and contractile response of dispersed circular smooth muscle cells stimulated by Ach in model group were declined obviously than the control(P<0.05) while the levels of serum CCK, iNOS mRNA expression and NO production were significantly elevated(P<0.05). Conclusions: Elevated CCK secretion caused by CP up-regulated the expression of iNOS mRNA and increased the output of NO within the gastrointestinal muscularis. It might be one of the mechanisms of gastrointestinal motility dysfunction in CP that NO inhibited the contractility of gastrointestinal circular smooth muscle. The trimebutine maleate can improve the gastrointestinal motility dysfunction caused by CP efficiently, by inhibiting the release of CCK.

Key words: chronic pancreatitis, gastrointestinal motility, cholecystokinin, NO