| Slow transit constipation(STC) is a chronic intractable constipation,which is characterized by measurably delayed movement of stools through the colon and hard stool. The prevalence of STC is higher in children. The pathophysiology of STC is unclear, with failure of clinical therapy.Interstitial cells of Cajal(ICC), are gastrointestinal pacemaker cells that play an vital role in gastrointestinal motility. The c-kit, a well-established marker for ICC, is critical for the development and maintenance of ICC networks. The exact pathophysiology of STC is barely understood but the ICC are generally believed to play an important role. Currently, the study about ICC in STC is mainly focused on colon, however STC is a full gastrointestinal motility disorder disease, so we think the ICC as an important role in STC disorders should not be limited to the colon.Prucalopride is a novel highly selective 5-HT4 receptor agonist developed for the treatment of chronic constipation among patients with an inadequate response to laxatives in our country. It is the most probable drugs for treatment of chronic constipation. The study found that 5-HT4 receptor has a positive effect for the volume recovery of ICC. After Prucalopride treatment, if there is influence to ICC which play an important role in STC,it has not been reported. The intention of this study was to observe the expression of c-kit m RNA in gastrointestinal tissues and moreover explore the role of ICC to the pathogenesis of STC. This study will also discuss the effect of prucalopride on ICC.32 healthy male Waster rats were chosen and divided randomly intotwo experimental group: normal control group(n=12), Rhein treatment group(n=20). Rhein suspension was administered intragastricly to established animal model of STC. The normal control group was intragastricted with normal saline. 4 rats in the normal control group and Rhein treatment group were gave activated Carbon, then sacrificed for carbon movement to validate the effectiveness of model. Then Rhein treatment group were randomly divided into model control group and prucalopride treatment group(treatment group), 8 rats in each group. In treatment group, prucalopride was administered intragastricly 2 weeks. The normal control group and model control group were intragastricted with normal saline. At the end of experiment, rats were sacrificed. Expression level of c-kit m RNA in gastrointestinal tract was determined by RT-PCR.Result of clinical symptoms: rats in normal control grouphas hair luster, spirit was good, the activity was normal. Rats in Rhein treatment group decreased activity and has poor spirit, piloerection, diarrhea symptoms, lower body weights. The actived carbon pushing rate of Rhein treatment group was significantly shorter than in the normal control group(38.70±3.55 vs 61.55±2.31, P<0.05). So we can conclude that STC model successed. The expression of c-kit m RNA in intestinal and colon were significantly lower in the model control group than in the normal control group(0.38±0.01 vs 0.90±0.04,0.32±0.03 vs 1.03±0.08, P<0.05), but there were no significant difference in the gastric antrum(0.61±0.07 vs0.67±0.02, P>0.05). Given prucalopride treatment 2 weeks, the hair, spirit,activity, body weight and actived carbon pushing rate were improved compared with model control group(60.96±8.59 vs 39.31±4.60, P<0.05).And the expression of c-kit m RNA in colon was significant differences with model control group(0.85±0.06 vs 0.32±0.03, p<0.05), but not in gastric antrum and intestinal(0.40±0.02 vs 0.38±0.01, 0.65±0.02 vs0.61±0.07, P>0.05).We can had the conclusion that: The significantly reduction of c-kitgene in intestinal and colon tissue may play an important role in the pathogenesis of STC, but the expression of c-kit gene in gastric antrum are no significant correlation with STC. Prucalopride can enhance the expression of c-kit m RNA in colon, promote recovery of the ICC to achieve the function of treating the STC. |
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