| Irritable bowel syndrome is one of the disorders of gastrointestinal function,with the characteristic of abdominal pain or discomfort,associated with characters change and habit change in stool.Although the IBS patients have discomfort in abdominal,there are no pathology or organic change.In additional,the IBS patients always afflicted with mental anguish,emotional fragility,poor quality of sleep,anxiety,depression,especially the patients seek for treatment repeatedly.Too much stress,anxiety or depression cause abnormal gastrointestinal function mainly.Epidemiological survey shows that IBS patients are mostly middle aged of twenty to forty years old,the proportion of female are higher than male.The global prevalence of IBS is five to twenty five percent,the Asian countries account for five to ten percent.IBS has a longer duration and recurrent repeatedly,which seriously affected the quality of life of patients,and takes up a lot of medical resources.Valeriana jatamansi Jones is a bind multi-ethnic herbal medicine in Yunnan,which were record in pharmacopoeia of 2010 edition.Our study was based on the theory of TCM,the civilian applications and modern pharmacology of Valeriana jatamansi Jones.Initially,Valeriana jatamansi Jones and its Iridoid constituents were found could improve the visceral hypersensitivity,gastrointestinal dysfunction and psychomotility in IBS rats established by being exposed to chronic unpredictable mild stress.The mechanism is related to the regulation of 5-HT in both gastrointestinal system and central nervous system.In the latter stage,we separated the monomer ZXX and ZXY form Iridoid constituents,and found that both ZXX and ZXY had effect on three mice models of diarrhea.In additional,both ZXX and ZXY could inhabit the shrink effect of colon cell caused by 5-HT.In this study,we observed the influence of ZXX and ZXY on visceral hypersensitivity,gastrointestinal dysfunction and psychomotility of IBS rats to evaluate the treatment effect of IBS,and to detection the change of Trp 5-HT,5-HIAA,the activity of TPH and MAO-A and the expression of 5-HTR in brain of IBS model rats to explore the regulation of ZXX and ZXY on the pathway of 5-HT in CNS.1 Research on the therapeutic effect of ZXX,ZXY on IBS model rats established by chronic unpredicted mild stress1.1 Establishment of a model of irritable bowel syndrome in rats by exposing to chronic unpredictable strssorsMethod:140-160g SD male rats were randomly divided into 10 groups:control group,model group,ZXX high,medium and low dose group(1.2,0.6,0.3 mg/kg),ZXY high,medium and low dose group(0.6,0.3,0.15 mg/kg),fluoxetine group(2.5 mg/kg)and the Pinaverium Bromide(25 mg/kg)in the study.The model was established by CUMS and independent feeding for 9 weeks.The animals of control group were housed 7-8 in a cage without any stimulation.Assessed visceral sensation by abdominal withdrawl reflex(AWR)valve pressure and assessed gastrointestinal motility by counting the feces granules.Open-field test and fluid consumption test were used to evaluate the neuropsychic fuction of animals.1.2 Effect of ZXX,ZXY on visceral hypersensitivity and gastrointestinal function of IBS established by chronic unpredicted mild stress(CUMS)Abdominal withdrawl reflex(AWR)scores and latency period of defecation were used to evaluate visceral hypersensitivity and gastrointestinal function of IBS.The study found that AWR scores and latency period of defecation had no significantly statistical meaning in each group of rats before establish IBS model.After IBS model established,the AWR scores significantly increased and latency period of defecation significantly shorter.ZXX,ZXY could decrease AWR scores and prolong latency period of defecation.1.3 Effect of ZXX,ZXY on spiritual activity function of IBS model rats established by CUMSSugar water predilection degree and weight change were used to evaluate spiritual activity function of IBS.The study found that sugar water predilection degree and weight change had no significantly statistical meaning in each group of rats before established IBS model.After making IBS model,the sugar water predilection degree and weight change were significantly decreased.ZXX,ZXY could increase sugar water predilection degree and weight change.2 Research the regulation of TPH2mRNA on the path way of 5-HT in CNS of IBS model rats established by CUMS2.1 Effect of ZXX,ZXY on the synthesis path way of 5-HT in CNS of IBS model rats established by CUMSThe study found that the quality of 5-HT were significantly decreased in cerebral cortex,hypothalamus and hippocampus.The express of TPH2mRNA in brain stem was increased significantly.Therefore we presumed that the increased express of TPH2mRNA was a compensatory response to the fall of 5-HT in central under a long term CUMS.Thereby future speculated that the fall of 5-HT in central was not induced by regulated by the synthetic of TPH2,on the contrary the decrease of 5-HT was promoted the expression of TPH2mRNA.ZXX,ZXY could promoted the level of 5-HT in cerebral cortex,hypothalamus and hippocampus and inhabited the express of TPH2mRNA in brain stem,which suggest that the mechanism of the therapeutic effect of ZXX,ZXY could related to the change of 5-HT in CNS.2.2 Effect of ZXX,ZXY on the metabolism of 5-HT in CNS of IBS model rats established by CUMSThe study found that the quality of 5-HI A A were significantly decreased,and the conversion rate of 5-HT was significantly decreased in cerebral cortex of IBS model rats.The quality of 5-HIAA was no significantly statistical change in each group,but the conversion rate of 5-HT was significantly decreased in hypothalamus of IBS model rats.The activity of MAO-A was significantly increased in hippocampus of IBS model rats,which suggest that the increased conversion rate of 5-HT could related to the increase activity of MAO-A,the speed up of the metabolism of 5-HT may caused the abnormal of spiritual activity function of IBS model rats.ZXX could significantly inhabit the conversion rate of 5-HT in cerebral cortex and hypothalamus,ZXY could significantly inhabit the conversion rate of 5-HT in cerebral cortex.ZXX,ZXY could significantly inhabit the activityof MAO-A in hippocampus.2.3 Effect of ZXX,ZXY on the express of 5-HT3mRNA of IBS model rats established by CUMS in CNS5-HT3 receptor could start brain-gut interaction by transport the enteric nervous signals to brain.5-HT3 receptor primarily bind to 5-HT to cause abdominal discomfort,visceral hypersensitivity and gastrointestinal abnormalities in IBS patients and could impact the mental emotions such as depression,anxiety through regulation of neurotransmitter.The study suggest the express of 5-HT3AR mRNA significantly increased in hippocampus of IBS model rats,the middle dose of ZXX and ZXY could decrease the express of 5-HT3AR mRNA in hippocampus,which suggest that the effect of ZXX and ZXY on visceral hypersensitivity and spiritual activity function could related to 5-HT3AR mRNA in CNS.ConclusionsTo use abdominal with drawl reflex scores and pressure threshold to evaluate gastrointestinal function of IBS,use latency period,grains and moisture of defecation to evaluate gastrointestinal function of IBS,use Sugar water predilection degree and weight change were used to evaluate spiritual activity function of IBS,which greatly increased the credibility of pharmacodynamic evaluation.ZXX and ZXY could improve visceral hypersensitivity,gastrointestinal dysfunction and spiritual activity function of IBS model rats and the mechanism may was the regulation of the path way of 5-HT in CNS. |
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