Effects Of Paroxetine And Ketotifenin On The Visceral Sensitivity In Rats With Low Grade Inflammation Of Colonic Mucosa Induced By DSS

Objective:To establish a model of rat with low grade inflammation in colonic mucosa and investigate the changes of visceral sensitivity, and the role of paroxetine and ketotifen on reducing hypersensitivity in these rats.Methods:Forty-eight male SD rats were randomly divided into two groups by 1∶5,8 rats in control group(group A) were free to drink distilled water for 7 days then were intragastriced with distilled water for another 7 days. 40 rats in experimental group(group S) were given 1.5%DSS solution for 7 days. And at the eighth day, the 40 survival rats were randomly divided into 5 groups, 8 rats in each group, that is: rats in Group B were intragastriced with distilled water for anther 7 days, Group C with paroxetine 5mg/Kg.d and group D with paroxetine 2.5mg/Kg.d for 14 days, Group E were intragastriced with ketotifen 1mg/Kg.d and Group F with ketotifen 0.5mg/Kg.d for 7 days. The abdominal myoelectric activities(AMAs) were recorded. The expressions of 5-HT and SERT, and the changes of mast cells(MC) in the colonic mucosa were detected by immunohistochemistry and toluidine blue staining respectively.Results:The AMAs in group B with colonic distention by 40,60,80mmHg were 36.271±7.197, 47.737±14.952 and 59.139±13.155 (μv) respectively, and were significantly higher than those in control group (22.975±6.150, 28.890±7.360 and 33.797±8.416, p<0.01). There was no significant difference among group D, E, F and group A(p>0.05). However, the AMAs in group C were significantly higher than in group A. The 5-HT average gray scale(AGS) in the distal colon in group B was 102.4876±9.310, which was lower than that in group A (123.694±10.372, p<0.01). 5-HT AGS were no significantly different between group D and A(p>0.05). SERT AGS in group B, C were significantly increased compared with group A (p<0.05). There was no significant difference of SERT between group D and A(p>0.05). The numbers of MC were 5.250±2.252 in group B, which was significantly higher than those in group A (2.250±1.488, p<0.05). The degranulation rates of MC were 0.601±0.221 in group B, and also significantly higher than those in group A (0.348±0.173, p<0.05). There was no significant difference among group E, F and group A(p>0.05).Conclusion:Visceral sensitivity increased in rats with low grade inflammation of colonic mucosa. Low dose of paroxetine attenuated visceral hypersensitivity by regulating the expressions of 5-HT and SERT, while ketotifen by stabilizing mast cell.