替加色罗对便秘型肠易激综合征大鼠模型肠道功能和中枢c-fos表达的影响

目的研究替加色罗对便秘型肠易激综合征（C-IBS）大鼠模型排便、肠道敏感性和中枢神经c-fos表达的影响。方法应用冰水灌胃方法建立C-IBS大鼠模型20只，随机分为替加色罗药物组（A组）和对照组（B组）。A组给予室温20％替加色罗溶液（2mL／只，1次／日）灌胃7d；B组给予等量室温生理盐水灌胃7d。观察灌胃期间两组大鼠灌胃后3h内和3～24h间的大便粒数及含水量变化，停止灌胃后继续观察7d内大便粒数及含水量变化。第14d实验结束后所有大鼠给予直肠内球囊扩张，检测球囊扩张引起腹部收缩反射的最小容量阈值及球囊不同容量扩张时腹部收缩反射的次数，以评价替加色罗对肠道敏感性的影响。脊髓、下丘脑及前扣带回c-los表达应用免疫组织化学染色及计算机图像分析系统半定量分析。结果两组大鼠灌胃后3h内大便粒数及含水量无明显差异（P〉0．05）；A组灌胃后3～24h间的大便粒数及含水量均较B组明显增加（P〈0.05）。直肠内球囊扩张时，A组引起腹部收缩的最小容量阈值略低于B组，无明显统计学差异（P〉0．05）。直肠球囊扩张体积1．0mL时A组腹部收缩反射次数高于B组（P〈0．05）；体积1.5mL、2．0mL高容量扩张时两组无明显差异（P〉0．05）。A组腰骶段脊髓背角、下丘脑和前扣带回的C-fos阳性神经元细胞的面积及OD值均明显低于B组（P〈0．05）。结论替加色罗能改善便秘型肠易激综合征大鼠模型的便秘和肠道敏感性，并减少脊髓、下丘脑及前扣带回c-fos的表达。

The effect of Tegaserod on the bowel function and expression of c-fos in central nerves system of constipation predominant irritable bowel syndrome rat model

Objective To study the effect of tegaserod on the constipation and bowel sensitivity in the rat model of constipation predominant irritable bowel syndrome (C-IBS),and to detect the c-fos expression of central nerves system (CNS) in order to elucidate the possible central mechanism in the process.Methods Twenty wistar rats of C-IBS model were divided into two groups: group A (stomach irritation of 20% tegserod solution,2 ml/d) and group B (stomach irritation of room temperature water).All the rats received stomach irritation daily for seven days,and the feces granules of rats were counted during 0 to 3 hour and 3 to 24 hour,and the moisture contents of the feces were calculated daily in corresponding period for 14 days.In 14 d,with the method of rectal balloon distention,the perception thresholds and the number of abdominal withdrawal reflexes (AWR) of different balloon volume were observed.The expression of c-fos in CNS was detected by immunohistochemistry methods,and analyzed semi-quantitively by computerized image analysis system.Results There was no difference of granules and moisture contents of feces during 0 to 3 hour after irritation between two groups,while the above items of group A were found significantly higher compared with group B during 3 to 24 hour (P<0.05).The perception threshold of group A was slightly lower than that of group B,but there is no significant difference statistically(P>0.05).At the same time,The number of AWR to the lower balloon content (1.0 ml) was higher in group A than that in group B(P<0.05),though no difference was found to the higher balloon content (1.5 ml and 2.0 ml).Besides,the areas and OD value of c-fos positive neurons in group A were significantly lower than those of group B(P<0.05).Conclusion Tegaserod can modulate the bowel sensitivity as well as improve the constipation in the C-IBS rat model induced by stomach irritation of cool water.Lower expression of c-fos in CNS is probably involved in the process.