| Background and objectives Irritable bowel syndrome (IBS) is a kind of common functional gastrointestinal disorder in clinic, but the mechanism has not been clarified so far. Presently it has been known that visceral hypersensitivity is one of the most important pathophysiological mechanisms of IBS. Stress may lead to visceral sensitivity abnormalities, especially anxiety is likely to be closely associated with visceral hypersensitivity, but the definite mechanism is unclear. Stress/anciety can activate hypothalamic-pituitary-adrenal axis (HPA axis), which induces the releasing of corticotropin releasing factor (CRF) in centrum and then the increasing of glucocorticoid (main cortisol) content in blood. So some scholars speculate that under stress, glucocorticoid hypersecretion through HPA axis may induce the high reaction of colon for the stimulation of distention by acting on centrum. Besides, perhaps CRF results in anxiety and visceral hypersensitivity through other routes except HPA axis. SaintJohn's Wort Extracts (trade name: Lu You Tai) is a kind of anti-depression and anti-anxiety drugs, and we have found it can effectively improve syndromes of IBS patients. The aim of our study was to evaluate the role of anxiety incolorectal sensitivity in rats, the relatiomship between serum corticosterone and visceral hypersensitivity and the efficacy of anti-anxiety treatment on improvement of visceral hypersensitivity. Moreover, to discuss mechanisms of anxiety inducing visceral hypersensitivity and anti-anxiety drugs produce curative effect. Our study offered new ideas and clues for further researching the mechanism of anxiety inducing visceral hypersensitivity, and found a new method for the improvement and treatment of IBS.Methods (D 48 Wistar rats (two month, 250~280g) were randomly averagely divided into 3 groups, the control group, the anxiety group and the drug-treated group. A chronic emotional stress model which main behavior was anxiety was established by empty bottle stimulation lasting 2 weeks. ? In 14 days of stress, Saint.John's Wort Extracts was administered to drug-treated rats, and 0.9 % sodium chloride was administered to anxiety and control rats (all were gastogavaged once daily). While the stressor was given, we observed and analysed behavioral changes of rats including attack, explore and embellishment. (D The visceral sensitivity to colorectal bolloon distention (CRD) was measured by abdominal withdrawal reflex scores (AWR scores). (D Each group was averagely divided into the CRD group and the non-CRD group, CRD was performed in CRD group. ?The corticosterone content in serum was evaluated by radioimmunoassay.Results (D Embellishment behavior of control rats was 1.83 ±0.17 times, anxiety rats only was 0.33 ±0.17 times, and the time of the latter decreased (P<0.01). Explore and Attack behaviors of control rats were averagely 0.24 ±0.18 and 0.00 ± 0.00 times, anxiety rats were 2.61 ±0.25 and 3.29±0.31 times, and the time of the latter manifolded (P<0.01). After anti-anxiety treatment with Saint.John's Wort Extracts for 2 weeks, Embellishment, explore and attack times separately were 0.67 ± 0.32, 2.43 + 0.35 and 2.14 ±0.33. Compared with anxiety rats, embellishment behavior increased and attack behavior decreased (P<0.01), but explore behavior wasn't significantly affected by Saint.John's Wort Extracts and only had a slight decreased (P>0.05). Three behaviors still increased compared with controls (P<0.01). (D AWR scores were significantly high under all CRD pressures (20, 40, 60, 80mmHg) by stress, compared with controls (P<0.0\). The scores increased from 0.00 to 2.00 under 20mmHg pressure, from 1.25 to 3.00 under 40mmHg, from 2.25 to 4.00 under 60mmHg, and from 3.25 to 4.00 under 80mmHg. In these anxiety rats, 14 rats accounting for 87.5 % were scored 2 or more under 20mmHg pressure, 3 rats were scored 4 under 40mmHg, and 12 rats were scored 4 under 60mmHg, accounting for 75%. AWR scores in drug-treated rats were significantly low under CRD pressures (20, 40, 60mmHg), compared with anxiety rats (P<0.01). The scores separately were 0.25, 1.50 and 2.5, which were not significantly different with controls (P>0.05). However, AWR score in drug-treated rats under 80mmHg averagely was 4 as same as anxiety rats (P>0.05). (3) The level of corticosterone in serum in the control group averagely was (535.96+36.54) ng/ml, and the anxiety group was (877.89±38.49) ng/ml. The latter significantly increased (P<0.01). But the level of corticosterone in serum wasn't significantly affected by Saint. John's Wort Extracts and only had a slight increase, which was (842.26 ± 27.60) ng/ml, compared with anxiety rats (P>0.05). In each group, the corticosterone content in CRD group wasn't significantly affected by CRD and only had a slight increase, compared with non-CRD group (P>0.05).Conclusions ? Axiety had effects on visceral hypersensitivity in IBS. The mechanism was not only due to differential activation of the HPA axis, probably related with the change of CRF and noradrenaline (NE) concentrations in brain. (2) Saint.John's Wort Extracts, possessing an anxiolytic-like effect, could improve visceral hypersensitivity, prior to treatment for anxiety. The mechanism was not probably due to differential activation of the HPA axis, probably related with the change of NE concentration in brain. |
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