| Objective:To explore the pathogenesis of irritable bowel syndrome(IBS) and the mechanism of curing experimental rat model of diarrhea-predominant IBS(D-IBS) in Tongxieyaofang.Methods:The animal we choosed is neonatal SD rats. Model rats of IBS were prepared by chronic stimulation in colon and stimulation on tails. The model was established by intrarectal stimulation of acetic acid daily in the neonatal rats between postnatal 8 and 21days for two weeks, weighting 10±2g. Then, stimulation on tails with forceps clip was given for 7 days. The threshold of abdominal withdrawal reflex (AWR) was evaluated during rectal distention at post 7, 9, and 10 weeks respectively, and the changes of rectal sensitivity were identified by the abdominal electrical activity measured at postnatal 12 weeks to prove the sucssess of the method of model.On the base of above successful model, model rats of IBS were randomly divided into six groups:the addition of the normal control group (Group A),the model group(Group B),the low dosage of Tongxieyaofang group (Group C),the middle dosage of Tongxieyaofang group (Group D),the high dosage of Tongxieyaofang group (Group E), with the Spasmomen control group(Group F).Different group received oral administration of different treatment in a different dose for one month with second in day.The respective dose of group A,B,C,D,E,F is 4ml/100g(40g/kg/d), 4ml/100g(40g/kg/d),0.4ml/100g(4g/kg/d),1.2ml/100g(12g/kg/d),4ml/100g(40g/kg/d),4ml/100g(150g/kg/d). And then , we should observe the bulgy capability of the sacculus that cause uplifting of abdomen and arching of back and the time of contract about abdomen muscle in rats. The level of vasoactive intestinal peptide (VIP), somatostatin(SS) in plasma and mucosa were evaluated. The Results were analyed by statistican.Results:1. In contrast to neonatal rats subjected to saline intrarectally (A group) and neonatal rats subjected to acetic acid intrarectally (B group), neonatal rats subjected to acetic acid intrarectally and stimulated with forceps clip on tails (C group) showed a significant decrease in the volume threshold of abdomen lifting and body arching during rectal distension(P<0.01). There was a significant increase of abdominal electrical activity responding to 0.3, 0.6, and 0.9mL distention volume. (Compared with B group P<0.05, P<0.05 and P<0.05, respectively. Compared with A group P<0.01, P<0.05 and P<0.05, respectively).2. After treatment, Tongxieyaofang and Spasmomen are able to make intestinal behavioral and electrophysiological indicators induced after sensitization returned to normal, there is no difference between the high dosage of Tongxieyaofang group and the group of Spasmomen. But there is no obvious recovery in the low dosage and the middle of Tongxieyaofang group.It can't reached statistical significance.3. The level of VIP in plasma of the model group rats increased significantly. The high dosage of Tongxieyaofang group and the group of Spasmomen were able to make the level of VIP descends significantly. There is no difference between the high dosage of Tongxieyaofang group and the group of Spasmomen. The level of VIP in mucosa of bowel of the model group rats increased significantly. The high dosage of Tongxieyaofang group and the group of Spasmomen were able to make the level of VIP in mucosa of bowel descend significantly. There is no difference in the two groups. The high dosage of Tongxieyaofang group and the group of Spasmomen were able to make the level of SS in plasma and mucosa of the model group rats descend significantly. But there is no mutation in the low dosage of Tongxieyaofang group, the middle dosage of Tongxieyaofang group.Conclusions:1. Chronic rectal irritation and stimulation with forceps clip on tails in the neonatal rats may lead to chronic rectal hypersensitivity in the adulthood. Stress and infection have synergistic effect in causing intestinal motility disorder. Stress makes the infective intestinal tract easier to be intestinal motility disorder, and the infective intestinal tract has stronger responding to stress. All those are in the absence of identifiable rectal pathological changes, which conforms to IBS.2. Both Tongxieyaofang and Spasmomen could correct the behavioral and electrophysiological indexes which changed to abnormal after intestinal allergy. The increase of VIP and SS content in plasma and colonic tissue played an important role in D-IBS pathogenesis. The balance of intestinal hormone VIP and SS were destroyed, which caused IBS at last.3. Tongxieyaofang could decrease the VIP and SS content in plasma and colonic tissue of model rats. The prescription eliminated the intestinal allergy by decreasing the effect of ACTH and recovering the balance of intestinal motility which increased the visceral pain threshold and normalized the intestinal hormone level.4. On the whole, the Therapeutic effects of Tongxieyaofang decoction and Spasmomen were similar, while the decoction effected better by high dosage. |
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