| Irritable bowel syndrome(IBS)is a kind of abdominal pain,diarrhea,abdominal discomfort and bowel habits and stool changes as the main clinical manifestations of functional gastrointestinal disorders,but its lack of explanation of symptom specific biochemical and morphological abnormalities.At present,IBS has become a global disease,although China's prevalence rate is slightly lower than the western countries,but it is still increasing year by year.The long-term and recurrent attacks of the disease have a serious impact on the quality of life of the patients,and lead to high medical costs and a heavy family economic burden.Therefore,the study of irritable bowel syndrome is an urgent problem to be solved.However,the pathogenesis of irritable bowel syndrome is unclear,mainly related to genetic inheritance,gastrointestinal motility abnormality,visceral hypersensitivity,brain gut axis abnormalities,intestinal flora imbalance,intestinal infection,bile acid metabolism abnormality and mental factors.Currently on the market for conventional drugs for the treatment of IBS mainly include antispasmodic,antidiarrheics,cathartic,etc.,can be used to relieve the clinical symptoms of IBS patients with abdominal pain,constipation,diarrhea,but because of serious side effects and limited clinical application.Traditional Chinese medicine is unique in the treatment of IBS.In order to harmonize the liver and spleen and eliminate dampness and regulate qi,some traditional Chinese medicine or traditional Chinese medicine compound has achieved obvious curative effect in the tratment of IBS,such as root of kudzu vine,ramuli umcariae cum uncis,Xiaoyao San,tongxieyao formula,suppressing liver and helping spleen soup and so on.Valerianae Jatamansi Rhizoma et Radix sweet known as Patrinia herb(Valeriana jatamansi Jones)v.jatamansi dried rhizome and roots,is contained in "China Pharmacopoeia"2015 Edition(a).The main efficacy:disperse food to suppress purge,regulate qi and relieve pain,dispel wind and eliminate dampness,calm terror and mind.It mainly used in the clinical treatment of abdominal distention,dyspepsia,diarrhea,dysentery,rheumatism,insomnia and other symptoms.Our previous study found that both the original powder and iridoid effective parts could reduce the visceral sensitivity of IBS rat model caused by chronic stress,significantly reduce the amount of defecation in IBS model rats,improve the mental state and has obvious analgesic effect,its mechanism may be related to regulation and 5-HT,gastrointestinal hormones and mast cells the immune system.ZXX and ZXY have the effect of improving visceral hypersensitivity,gastrointestinal hyperfunction and abnormal function of mental activity,mechanism of action may be of clinical symptoms and relieve IBS by downstream factor and influence of MC and PAR2 on the regulation of colon colon 5-HT,can significantly improve the mental state of mice diarrhea induced by reserpine and abnormal effect.However,the preparation process of monomer components is more complicated and not suitable for large production.In order to facilitate development and utilization,this experiment uses a relatively simple preparation of spider incense extract(macroporous resin elution enrichment)as a trial drug,and studies its effect and mechanism on the IBS model rats with three kinds of stress induced by mother to child separation.The animal model of IBS in the past is focused on the simulation of IBS symptoms such as visceral hypersensitivity,increasing frequency of defecation,and abnormal mental state in adult rat model.However,children who are troubled by early negative life events,of which children of 18-61%will be in adulthood.The symptoms of IBS appear.Therefore,for the replication of IBS model,we should pay attention to the important pathogenic factors of early life negative events.In addition,the study of the mechanism of Valeriana jatamansi Jones is focused on some molecular mechanisms such as abnormal intestinal motility,abnormal visceral sensation,or abnormality of the brain-gut axis,and lack of understanding of the interaction and interaction of multiple elements.As a more important part of system biology,metabonomics has become a hot spot of research.Metabonomics is used to study endogenous metabolites with relative molecular mass below 1000 in organisms,and the science of dynamic changes of these metabolites under internal and external influences.The most important feature of metabonomics is through high throughput experiments and large-scale calculations.From the perspective of system biology,the metabolic changes of the body are comprehensively investigated,and the mechanism of the occurrence and action of the organism is discussed from the point of view of the whole.Therefore,on the basis of the separation of three stress IBS rats and the separation of mother to baby.By means of metabonomics,we analyzed the metabolic pathways of small molecule metabolites,and explored the Valeriana jatamansi Jones extract to neonatal maternal separation(NMS)from the whole point of view.The mechanism of the effect of infant separation combined with three kinds of stress on IBS rats.Objective:In order to therapeutic effect and mechanism of IBS in the rat model of v.jatamansi extract on maternal separation combined with three kinds of stress,through this experiment,IBS rat model of maternal separation combined with three kinds of stress,to observe the changes of rat model of visceral sensitivity,fecal and mental activities,to evaluate the therapeutic effect of v.jatamansi extract on IBS research focus;based on metabonomics,analysis of changes in the serum and fecal metabolites and related regulation pathways,to explore the mechanism of the extract of v.jatamansi IBS rats maternal separation combined with three kinds of stress.Methods:1.SD rats were randomly divided into control group,IBS model group,v.jatamansi extract high,medium and low dose group,Zhengchangsheng group and pinaverium bromide group,12 rats in each group.IBS rat model was established by maternal and child separation combined with three kinds of stress.The dosage group of the spider incense extract and the positive drug groups were given the medicine daily for the ninety-first days.The control group and the model group were given the distilled water of the stomach.Abdominal reflex pressure threshold was used to evaluate the changes of visceral sensitivity,fecal water content was used to evaluate stool traits in rats,and the immobility time of rats in forced swimming test was used to evaluate the changes of mental activity in experimental animals.2.The therapeutic effects of spider extract on IBS model of three kinds of stress combined with mother to child separation were investigated by determining the threshold value of abdominal reflex reflex,fecal water content and forced swimming test.On the thirty-fifth,eighty-sixth,105th,122nd day of experiment,we measured the pressure threshold of abdominal reflex reflex in experimental rats.We measured the fecal water content of experimental rats on the thirty-seventh,eighty-eighth,108th,125th day of experiment,and measured the forced swimming test of thirty-eighth,eighty-ninth,107th,124th of experiment.3.The excrement and serum samples of rats were detected by metabonomics,and the changes of metabolites and related regulatory pathways were observed.Results:1.The thirty-fifth,thirty-seventh,thirty-eighth day of the experiment,the rats Abdominal withdrawal reflex threshold pressure,fecal water content,forced swimming test results have no significant difference(p>0.05);the ninetieth day of the experiment,the model rats Abdominal withdrawal reflex threshold pressure lower than that of the control group(p<0.05),fecal water content and the immobility time was significantly higher than that of the control group(p<0.05).After the treatment of spider extract,the abdominal reflex pressure threshold of each treatment group was significantly higher than that of the model group(p<0.05),and stool water content and forced swimming test immobility time were lower than those of the model group(p<0.05).2.The IBS model of mother to child separation combined with three stress was successful.Compared with the control group,the levels of metabolites in the stool samples of rats in the model group changed,resulting in the disorder of their metabolic pathways.After multidimensional,single dimensional statistical analysis and mzCloud spectrum matching,Chemspider,Metlin and HMDB and Kegg Pathways database search,71 metabolites were identified,of which 38 metabolites showed a significant down-regulation,and 33 metabolites showed a significant increase.Up regulation of metabolic pathways involved in main bile acid metabolism,primary bile acid biosynthesis,phenylalanine metabolism,the down regulated metabolic pathway mainly in steroid hormone synthesis,linoleic acid,arachidonic acid metabolism,sphingolipid metabolism,ceramide synthesis.After the treatment of spider aroma extract,and reduce visceral sensitivity in rats model of the depression improved,diarrhea symptoms improved,metabolite levels in fecal samples have undergone a series of changes,there were 76 metabolites,39 metabolites showed a significant down-regulation,37 metabolites showed a significant difference increase.The metabolic pathway was significantly increased in the model group such as primary bile acid biosynthesis,bile acid metabolism,phenylalanine metabolism and metabolic pathway down down,in the model group such as linoleic acid,four arachidonic acid metabolism,sphingolipid metabolism,ceramide synthesis appeared significantly raised.3.The IBS model of mother to child separation combined with three stress was successful.Compared with the control group,the levels of metabolites in the serum of the model group changed,resulting in a disorder of the related metabolic pathways.The content of serine,threonine,leucine,arginine,proline decreased,increased the content of phenylalanine,tyrosine,tryptophan,resulting in reduced arginine proline metabolism,short chain fatty acid pathway,tryptophan,cysteine metabolism increases,changes in these metabolic pathways may lead to an important factor in the pathogenesis of IBS.After the treatment of spider aroma extract,metabolite levels in serum samples have undergone a series of changes,decreased serine threonine and leucine,arginine,proline content increased significantly,while the serine and betaine increased inhibition of cysteine metabolism pathway of tryptophan metabolism in 5-HT level decreased significantly,so as to improve the IBS rat visceral hypersensitivity and other adverse symptoms.Conclusion:The visceral sensitivity of IBS rats in this experiment using the Abdominal withdrawal reflex threshold pressure index to evaluate maternal separation combined with three kinds of stress;the fecal water content evaluation of defecation in rats by forced swimming test;real time evaluation of rat's mental state;the pharmacodynamics evaluation index.The results show that the three stimulation of mother to child separation combined with tail clamping,restraint and ice water swimming can lead to increased visceral sensitivity,diarrhea and mental activity in IBS rats.The spider extract can improve maternal and infant separation combined with three stress IBS models in the IBS model of rat visceral sensibility,diarrhea and mental activity abnormalities.The mechanism may be related to the regulation of tryptophan metabolism,short chain fatty acid metabolism,arginine proline metabolism,steroid hormone synthesis and phenylalanine metabolism.This experiment provides experimental evidence for studying the material basis and action mechanism of spider IBS in the treatment of IBS,and provides a new idea for the research of new drug in the treatment of IBS. |
PDF Full Text Request