| Objective: To establish a new concept model of irritable bowel syndrome with predominant-constipation(C-IBS) in rats, and to study the expression of 5-hydroxytryptamine(5-HT) and c-fos in this model and their possible roles in the pathophysiology of IBS.Methods: 50 Wistar rats of postnatal four weeks were divided into three blocks randomly. Group A: 2.0ml of ice water at 0-4 C was given intragastrically once a day for 2 weeks respectively; Group B: 2.0ml of water with room temperature was given intragastrically once a day for 2 weeks respectively; Group C: control group. The granule number and the moisture content of the feces from all groups were recorded daily after gavage during 0 to 3 hour and 3 to 24 hour respectively for 28 days. At the end of 4 weeks, the rectal balloon distention were performed to evaluate the perception thresholds and the abdominal withdrawal reflex. The colon samples in ileocecal junction and distal colon were stained by haematoxylin-eosin for the routine pathologic examination and toluidine blue for mast cells. The expression of 5-HT and c-fos in colon and central nervous system(CNS) were showed by immunohistochemistry and were analyzed by computing image analysis system semi-qualitively. Results: The feces granule and moisture content were significantly elevated in group A than in group C after gavage during 0 to 3 hour (P<0.05), but this phenomenon disappeared when the gavage stopped. The feces granuleand moisture content were significantly elevated in group A than in group C after gavage during 3 to 24 hour (P<0.05) , and the phenomenon lasted for 4 weeks in spite of the gavage stopped in second 14 days(P<0.05). The perception threshold of group A was higer than that of group C during rectal balloon distention, but no there is no significant differences statistically (P>0.05). The numbers of abdominal withdrawal reflex to the lower balloon content (1.0ml) were 10.3+3.3 within 3 min, significantly less in group A than in group C(18.3+5.5), P<0.05. The gastrointestinal pathologic were not abnormal in all rats. The number of mast cells of ileocecal junction and distal colon were 12.61+4.81/HP and 10.21+3.03/HP in group A, significantly more than in group C in which were 7.91+3.40/HP and 4.97+2.07/HP(P<0.05). The 5-HT immunoreactive cells were detected in colon and CMS which were in the mucasa ECs and myenteric nerve plexus of ileocecal junction and distal colon, laminael I and II of the dorsal horn in L5-S2 segments, cingulate gyrus and hypothalamus. According to image analysis, the opacity density(OD) and areas of 5-HT immunoreactive positive cells were markedly higher in group A than in group C (P<0.05). The c-fos immunoreactive positive neurons and fibres were found in the above regions as well and demonstrated the similarly expressions to the 5-HT. Meanwhile, the correlation analysis showed that the expression of 5-HT and c-fos existed close relation in group A (r=0.6049-0. 7945, P<0. 05). Conclusion: A new concept model of IBS is created which characterized with constipation, change of bowel sensitivity, and increase of MCs and 5-HT positive endocrinal cells. On this new model, expression of 5-HT and c-fos are abnormal in bowel and nervous tissue. The results suggest thatIntestinal MC, 5-HT postive enterendocrine cells and nervous fibres in ENSand CMS may be involved in the bowel dysfunction. 5-HT may play animportant role in brain-gut axis in which mediates the nociceptivetransmission from bowel to CMS. The expression of c-fos may be due to theabnormity of 5-HT in nerves system. |
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