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Irritable bowel syndrome(IBS)is one of the most common functional gastrointestinal disorders,of which diarrhea-predominant IBS(IBS-D)accounts for the largest proportion.The pathogenesis of IBS-D is complicated and diverse,and there is currently a lack of clinically effective drugs.The establishment of animal models is an essential tool for further studies of the disease mechanisms,evaluation of clinical efficacy,and drug development,and the preparation and evaluation standards of models are important factors affecting the quality of the research.Based on the currently accepted pathogenesis of IBS-D and the previous modeling experience of our research group,this review systematically summarizes the evaluation method used in animal models of IBS-D in terms of diarrhea observation,visceral sensitivity tests,and intestinal motility tests,to provide a reference for future studies.
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Objective This paper summarizes and evaluates the existing animal models of Post-infectious irritable bowel syndrome(PI-IBS)based on the clinical diagnostic criteria and symptom characteristics of PI-IBS in Chinese and western medicine.The goal of this study is to seek out animal models with a high degree of clinical agreement between Chinese and western medicine,and to provide an accurate animal model for the prevention and treatment of PI-IBS in traditional Chinese medicine.Methods The animal strains,modelling methods,and mechanisms of the existing PI-IBS animal models were summarized based on the clinical diagnostic features and symptomatology of PI-IBS,as well as the degree of match was evaluated and the strengths and weaknesses of the preparation of animal models were analyzed,by reviewing the articles related to PI-IBS animal experiments and the preparation of animal models.Results A thorough analysis discovered that Campylobacter jejuni infection model,Trichinella infection model,and liver depression and spleen deficiency syndrome in models of disease and symptom combination showed a comparatively high level of clinical agreement between Chinese and western medicine.Conclusion The existing PI-IBS models had the high degree of coincidence with western medicine,Chinese medicine four diagnoses and syndrome are generally less embodied and collected in the modeling process.The primary symptoms in Chinese medicine diagnosis are primarily based on the observation of animal apparent behaviors,while the observation of the sub-syndrome manifestations is relatively less,which results in failure of judgment of TCM syndrome types.Therefore,it is still necessary to further standardize the criteria for evaluating symptoms and the techniques for identifying disease-syndrome combination animal models.PI-IBS model with the syndrome-clinical characteristics in Chinese and western medicine has significant application value and prospects in the future.The multifactorial composite method of western medicine pathological injury+Chinese medicine etiological stimulation can establish a PI-IBS model with a higher degree of coincidence,which can provide theoretical support for the study of the pathogenesis of PI-IBS,the difference of syndrome,and the prevention and treatment with integrative Chinese and western medicine.It is crucial to guide the clinical diagnosis and treatment of PI-IBS.
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Objective To observe the clinical efficacy of Lipi Qushi Recipe in the treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)of spleen deficiency and dampness superabundance type.Methods Seventy IBS-D patients with spleen deficiency and dampness superabundance type were randomly divided into an observation group and a control group,with 35 patients in each group.The control group was given oral use of Trimebutine Maleate Tablets,and the observation group was given Lipi Qushi Recipe.The two groups were treated for 4 consecutive weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,irritable bowel syndrome severity scoring system(IBS-SSS)scores,Hamilton anxiety scale(HAMA)scores,Hamilton depression scale(HAMD)scores,irritable bowel syndrome quality of life scale(IBS-QOL)scores,and serum interleukin 6(IL-6)level of the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy and safety of the two groups were evaluated.Results(1)During the treatment process,one case quitted spontaneously,3 cases fell off(failing in following the treatment schedule for some reasons),and one case lost to follow-up in the observation group;in the control group,3 cases quitted spontaneously and 2 cases lost to follow-up.Eventually,there were 30 patients in each of the two groups completing the full course of treatment.(2)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy in the observation group was 93.93%(28/30),and that in the control group was 80.00%(24/30).The intergroup comparison showed that the efficacy of TCM of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the TCM syndrome scores,IBS-SSS scores,HAMA scores,HAMD scores and IBS-QOL scores of the two groups were significantly decreased compared with the pre-treatment scores(P＜0.05),and the degree of the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the serum IL-6 level of patients in the two groups was decreased compared with that before treatment(P＜0.05),and the degree of the decrease in the observation group was significantly superior to that in the control group,with a statistically significant difference(P＜0.05).(5)In the course of treatment,no obvious adverse reactions occurred in the two groups of patients,with a high safety.Conclusion Lipi Qushi Recipe exerts certain effect for the treatment of IBS-D patients with spleen deficiency and dampness superabundance type,which can significantly alleviate the intestinal symptoms of the patients,reduce the intestinal inflammatory reaction of the patients,improve the anxiety and depression emotions,and improve the quality of life of the patients.
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Objective To observe the clinical efficacy of Modified Tongxie Yaofang(Important Formula for Relieving Diarrhea with Pain)in the treatment of patients with diarrhea-predominant irritable bowel syndrome(IBS-D)with liver-depression and spleen-deficiency syndrome.Methods Sixty patients with IBS-D of liver depression and spleen deficiency type were randomly divided into treatment group and control group,30 patients in each group.The patients in the treatment group were given modified Tongxie Yaofang,and the patients in the control group were given Pivacurium Bromide Tablets(Dicetel).Both groups were treated for a 4-week course of treatment.The changes of traditional Chinese medicine(TCM)syndrome scores,irritable bowel syndrome quality of life(IBS-QOL)scores,Hamilton Anxiety Scale(HAMA)scores of the two groups were observed before and after the treatment.Moreover,the efficacy for overall symptomatic improvement in the two groups was evaluated according to the grading of irritable bowel syndrome symptom severity score(IBS-SSS),and the efficacy for improving single symptom such as abdominal pain and diarrhea as well as the relapse after 4 weeks of drug cessation in the two groups were compared.Results(1)After 4 weeks of treatment,the total effective rate for overall symptomatic improvement in the treatment group was 83.33%(25/30),and that in the control group was 43.33%(13/30).The intergroup comparison(tested by chi-square test)showed that the efficacy for overall symptomatic improvement in the treatment group was significantly superior to that in the control group(P＜0.01).(2)After 4 weeks of treatment,the total effective rate for improving single symptom of abdominal pain and diarrhea in the treatment group was 80.00%(24/30),90.00%(27/30),and that in the control group was 43.33%(13/30),46.67%(14/30),respectively.The intergroup comparison(tested by chi-square test)showed that the efficacy for improving single symptom of abdominal pain and diarrhea in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After 4 weeks of treatment,the TCM syndrome scores,IBS-QOL scores,and HAMA scores of patients in both groups were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(4)After 4 weeks of drug withdrawal,the recurrence rate of the treatment group was 24.00%(6/25),which was significantly lower than that of the control group(61.54%,8/13),and the difference was statistically significant between the two groups(P＜0.05).Conclusion Modified Tongxie Yaofang exerts certain effect in treating patients with IBS-D of liver depression and spleen deficiency type,and the decoction is effective on decreasing the scores of symptoms of abdominal pain and diarrhea as well as TCM syndrome scores,improving the quality of life of the patients,and alleviating the anxiety status of the patients.
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BACKGROUND:As a common clinical digestive disorder,irritable bowel syndrome becomes an advantageous disease of acupuncture treatment.However,the therapeutic mechanisms remain unclear.The methodological characteristics of omics coincide with the multi-target and multi-level characteristics of acupuncture,providing the possibility of revealing the principle of acupuncture in the treatment of the disease. OBJECTIVE:To investigate the pathogenesis of irritable bowel syndrome with diarrhea(IBS-D)and the effect of acupuncture at the combined points(selected based on etiologies and symptoms)on IBS-D based on proteomics. METHODS:Twelve 3-month-old male Sprague-Dawley rats were randomly divided into three groups:a control group,an IBS-D model group and an acupuncture group.The IBS-D rat models were prepared using the CAS method.After successful modeling,bilateral Zusanli points,bilateral Neiguan points and Guanyuan points were selected for acupuncture treatment in the acupuncture group,with a frequency of 120 times/minute,1 minute of acupuncture every 4 minutes,and 15 minutes of needle retention,at an interval of 1 day every 6 days,for 28 days in total.Rats in the normal control group and the model group were not given any intervention.The pressure threshold of rat abdominal retraction reflex was measured to evaluate the visceral hypersensitivity of rats.Proteomics analysis was performed using the liquid chromatography-tandem mass spectrometry-based platform.MaxQuant software,Perseus software and DAVID,KOBAS,VENNY,STRING online tools were used for the bioinformatics analysis of proteomic data.Visualization analysis was done using Cytoscape 3.7.1 software. RESULTS AND CONCLUSION:There were 47 differentially expressed proteins between the IBS-D model and control groups.Function analysis of differentially expressed proteins revealed that the pathogenic mechanism of IBS-D was associated with abnormal energy metabolism,the imbalance of colon motor function and increased visceral sensitivity.Important proteins related to IBS-D pathogenesis included Atp5a1,Atp5c1,Idh3b,Atp2a3,Pdhb,Ppp1ca and Mapk3.Sixty-one differentially expressed proteins were identified between the acupuncture group and IBS-D model group.Acupuncture at the combined points reversed the up-regulation of nine differentially expressed proteins and the down-regulation of nine differentially expressed proteins.Bioinformatics analysis revealed that acupuncture at the combined points for IBS-D could function via multi-targets and multi-pathways,reverse the damage of energy metabolism caused by IBS-D,and play a role against oxidative stress and inflammation,thereby relieving pain and regulating the imbalance of intestinal function.Important proteins related to acupuncture effects included Atp5a1,Atp5c1,Pdhb,Sars,Uqcrc2,Prdx2,Prdx4,Ppp1ca,Manf and Tmsb4x3.All these findings preliminarily illustrate the potential molecular mechanisms of IBS-D and the effect of acupuncture at the combined points in the treatment of IBS-D at the protein level,which provide a basis for the clinical application of acupuncture at the combined points.
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ObjectiveTo investigate the mechanism of Akkermansia muciniphila （A. muciniphila） regulating the visceral hypersensitivity in irritable bowel syndrome （IBS） rats induced by neonatal maternal separation （MS） and water avoidance stress （WAS）. MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group （blank group）， MS+WAS group （IBS model group） and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile， the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group， A. muciniphila group exhibited significant increase of body weight and visceral pain threshold， significantly decreased numbers of fecal particles and proportions of unformed stools， significantly higher expression levels of cannabinoid receptor type 2 （CB2R） mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.
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ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome（IBS-C） rats before and after sweating. MethodIBS-C rat model was established by gavage of ice water， and rats were randomly divided into the blank group， model group， mosapride group（1 mg·kg-1）， M. officinalis cortex group（10 g·kg-1） and sweated M. officinalis cortex group（10 g·kg-1）. The changes of body weight， fecal number and fecal water content of rats were observed， 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats， the levels of 5-hydroxytryptamine（5-HT） and substance P（SP） in colonic tissues of rats were determined by enzyme-linked immunosorbent assay（ELISA）. ResultCompared with the model group， the fecal water content and fecal number of mosapride group， M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.05）. At the phylum level， the top four species of flora abundance were Firmicutes， Bacteroidetes， Spirochaetes and Proteobacteria. Compared with the blank group， the proportion of Firmicutes in the model group was significantly reduced（P<0.05）， while the proportion of Spirochaetes was significantly increased（P<0.05）. Compared with the model group， the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group， and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level， the top four species of flora abundance were Lactobacillaceae， S24_7， Ruminococcaceae， Bacteroidaceae， compared with the blank group， the proportion of Lactobacillaceae in the model group decreased significantly（P<0.05）， and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration（P<0.05）， and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level， the top four species of flora abundance were Lactobacillus， Unspecified_S24_7， Bacteroides and Treponema. Compared with the blank group， the proportion of Lactobacillus in the model group decreased significantly（P<0.05）， while the proportion of Treponema increased significantly（P<0.05）. Compared with the model group， ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group， indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group， the 5-HT content in mosapride group was significantly reduced（P<0.05）， the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.01）， and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group. ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.
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OBJECTIVE@#To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination".@*METHODS@#Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence.@*RESULTS@#Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group.@*CONCLUSION@#Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.
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Ratas , Femenino , Animales , Síndrome del Colon Irritable/terapia , Ratas Sprague-Dawley , Moxibustión/métodos , Frecuencia Cardíaca , Factor Natriurético Atrial , Puntos de Acupuntura , Ansiedad/terapiaRESUMEN
Objective To observe the difference in the expression of micro-ribonucleic acid(miRNA)in the colon tissue of irritable bowel syndrome-diarrhea(IBS-D)rats and rats treated with Jianpi Mixture,and predict The miRNA and corresponding genes involved in the treatment of IBS-D with Jianpi Mixture,providing a basis for finding potential therapeutic targets for IBS-D.Methods The rats were randomly divided into a blank group,a model group and a traditional Chinese medicine group,with 8 rats in each group.Both the model group and the Chinese medicine group used acute and chronic stimulation + senna leaf gavage to make the IBS-D model.The Chinese medicine group was gavaged with Jianpi Mixture after model building for 14 days.General condition,body weight and Bristol score were observed and recorded.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of colon in each group of rats.Transcriptome sequencing of rat colon tissue in each group to screen and map differentially expressed miRNAs.Perform GO(Gene oncology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis on the target genes corresponding to the screened common miRNAs.Results Compared with the model group,the weight of the rats in the Chinese medicine group increased significantly(P<0.01),and the Bristol score of the feces decreased significantly(P<0.01).The pathological damage of the colon tissue of rats in the Chinese medicine group was significantly reduced.Compared with the blank group,there were 109 differentially expressed genes in the model group,of which 80 were up-regulated and 29 were down-regulated.Compared with the model group,there were 109 differentially expressed genes in the traditional Chinese medicine group,of which 19 were up-regulated and 90 were down-regulated.Mapping the genes of the two comparisons found that 74 miRNAs in the model group were increased and 7 were decreased.The changes of these miRNAs were all reversed after the intervention of traditional Chinese medicine.The GO function enrichment analysis of target genes showed that Jianpi Mixture was mainly involved in synaptic vesicle positioning and transport,cytoplasmic transport,negative regulation of growth and development,and sugar transport after acting on rats.KEGG pathway enrichment analysis showed that MAPK,Wnt,Hippo,TNF,oxygen toxin,cAMP and other pathways were enriched.Conclusion After the intervention of Jianpi Mixture,IBS-D-related miRNA expression profiles have changed significantly;Jianpi Mixture may play a protective role in the treatment of IBS-D by regulating the MAPK signaling pathway and Wnt signaling pathway.Screening the core genes and predicting the miRNAs interacting with them provide a theoretical basis for the study of the pathogenesis of IBS-D and the therapeutic targets of Jianpi Mixture.
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ObjectiveTo explore the clinical efficacy and mechanism of Tongxie Yaofang in treating diarrhea-predominant irritable bowel syndrome（IBS-D） patients with liver depression and spleen deficiency. MethodA total of 168 IBS-D patients with liver depression and spleen deficiency who were treated from August 2017 to June 2021 were divided into observation group and control group by random number table，84 in each group. The observation group was administrated with Tongxie Yaofang decoction-free granules orally，and the control group received oral treatment of pinaverium bromide，both for 4 weeks. The main symptoms of IBS were compared before and after treatment，such as the degree of abdominal pain，stool changes，traditional Chinese medicine pattern curative effect scoring system（TCM-PES），IBS quality of life questionnaire （IBS-QOL），IBS symptom severity scale（IBS-SSS），self-rating anxiety scale （SAS），and self-rating depression scale（SDS）. Nimodipine was used to evaluate the efficacy based on TCM syndrome score of liver depression and Qi stagnation. Enzyme-linked immunosorbent assay（ELISA） was conducted to detect the plasma interleukin-10（IL-10）and IL-12 before and after treatment. ResultAfter 4 weeks of treatment， the response rate of abdominal pain in observation group was 92.86% （78/84）， higher than that in control group （82.14%， 69/84）（χ2=6.254，P<0.05）. The response rates of diarrhea in observation group and control group were 91.67% （77/84）and 77.38% （65/84）， respectively（χ2=8.214，P<0.01）. TCM-PES and IBS-QOL scores of observation group after treatment were higher and IBS-SSS score was lower than those of control group （P<0.05）. The efficacy rate of TCM syndromes in observation group was higher than that of control group （P<0.05）. Additionally， after treatment， the observation group had lower SAS and SDS scores （P<0.05）and IL-12 level（P<0.05）and higher plasma IL-10 level than the control group （P<0.05）. ConclusionTongxie Yaofang can relieve abdominal pain and diarrhea in IBS-D patients with liver depression and spleen deficiency，reduce negative emotion，and improve the quality of life of patients，which may be related to alleviating the visceral hypersensitivity.
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OBJECTIVE@#To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating @*METHODS@#A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating @*RESULTS@#After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (@*CONCLUSION@#Acupuncture for regulating
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Humanos , Terapia por Acupuntura , Diarrea/terapia , Síndrome del Colon Irritable/terapia , Calidad de Vida , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Bazo , Resultado del TratamientoRESUMEN
Objective:To establish an ultra-performance liquid chromatography-mass spectrometry （UPLC-MS/MS） for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration， and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome （CVH-IBS）. Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty （PTCA） balloon stimulation method. After intragastric administration of Wujiwan （0.245 g·kg<sup>-1</sup>）， blood was collected from the jugular vein at different time points， and the plasma concentrations of 10 active ingredients （berberine hydrochloride， palmatine hydrochloride， coptisine hydrochloride， jatrorrhizine hydrochloride， epiberberine， dihydroberberine， evodiamine， evodine， paeoniflorin， albiflorin） in Wujiwan was detected simultaneously by UPLC-MS/MS， the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group， the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent， and the peak time （<italic>t</italic><sub>max</sub>） was prolonged. Among them， the <italic>t</italic><sub>max</sub> of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute， respectively （<italic>P</italic><0.05， <italic>P</italic><0.01）. Area under the plasma concentration-time curve （AUC<sub>0-</sub><italic><sub>t</sub></italic>） of each component increased， and evodiamine and paeoniflorin were significantly different （<italic>P</italic><0.05，<italic> P</italic><0.01）. The clearance rates （CL/<italic>F</italic>） of these 10 active ingredients were all decreased， among which berberine hydrochloride， palmatine hydrochloride and evodiamine had significant differences （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats， which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.
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Objective:To explore the potential mechanism of Bianketong tablet （BKT） in the treatment of constipation-predominant irritable bowel syndrome （C-IBS） based on network pharmacology and bioinformatics. Method:The BKT-meridian network was constructed for analyzing the combined effect of the nine Chinese herbs in BKT. The active components and targets of BKT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and then screened according to the oral bioavailability （OB） and drug likeness （DL） criteria. Following the acquisition of C-IBS target set from GeneCards， Online Mendelian Inheritance in Man （OMIM）， Drugbank and DisGeNet， the protein-protein interaction （PPI） network was constructed. Cytoscape 3.7.2 was utilized for network visualization. The screened key targets were subjected to gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID platform. The C-IBS mouse model was established via intragastric administration of ice water， and the key targets of BKT against C-IBS were verified by enzyme linked immunosorbent assay （ELISA） and immunohistochemistry. Result:The large intestinal meridian was the main site where BKT acted. There were 70 potential active components in BKT， which acted on 227 intersection targets. Through T helper cell 17（Th17） differentiation， Toll-like receptor （TLR）， tumor necrosis factor and other signaling pathways， BKT participated in inflammatory response， immune regulation， intestinal nerve regulation， hormonal regulation， and oxidative stress response， thus exerting the therapeutic effects against C-IBS. As reveled by <italic>in vivo</italic> experiments， BKT significantly improved the small intestinal propulsion rate， up-regulated the expression of vasoactive intestinal peptide （VIP） in serum and colon tissue of C-IBS mice， and down-regulated the expression of nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， interleukin（IL）-6， and TLR2 in serum and colon tissue， which confirmed the reliability of integration analysis. Conclusion:BKT inhibits C-IBS via multiple components， multiple targets， and multiple pathways. This study has provided ideas for further clinical research and experimental verification of BKT in the treatment of C-IBS.
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Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities （No.1 and No.2） on irritable bowel syndrome （IBS） based on neuro-endocrine-immune network， and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine （TCM）. Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty （PTCA） in suckling rats. The animals were randomly divided into a control group， a model group， a dicetel group （0.01 g·kg<sup>-1</sup>）， low- （0.335 g·kg<sup>-</sup><bold><sup>1</sup></bold>）， medium- （0.67 g·kg<sup>-</sup><bold><sup>1</sup></bold>）， and high-dose （1.34 g·kg<sup>-</sup><bold><sup>1</sup></bold>） No. 1 Wujiwan groups， and low- （0.385 g·kg<sup>-</sup><bold><sup>1</sup></bold>）， medium- （0.77 g·kg<sup>-</sup><bold><sup>1</sup></bold>）， and high-dose （1.54 g·kg<sup>-</sup><bold><sup>1</sup></bold>） No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells （MC） in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine （5-HT）， substance P （SP）， somatostatin （SS）， and vasoactive intestinal peptide （VIP） in the blood/colon tissue were detected by enzyme-linked immunosorbent assay （ELISA） and immunohistochemistry （IHC） assay. Result:There was no significant difference in body weight among different groups. Compared with the control group， the model group exhibited decreased thresholds of abdominal elevation and bow back elevation （<italic>P<</italic>0.01）， increased density of MCs in the colon tissue （<italic>P<</italic>0.05）， up-regulated levels of 5-HT， SP， and SS in the blood and colon tissue （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and elevated VIP level in the colon tissue （<italic>P</italic><0.05）. Compared with the model group， Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation （<italic>P</italic><0.01）， diminish the count of MC in the colon tissue （<italic>P</italic><0.05）， and reduce the levels of 5-HT， SP， SS， and VIP （<italic>P</italic><0.05）. As demonstrated by the comparison of No. 1 and No. 2 Wujiwan， No. 1 was superior to No. 2 in reducing the concentrations of 5-HT， SP， and SS in the blood， especially in 5-HT （<italic>P</italic><0.01）. No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan， No. 2 significantly reduced SP expression， and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups （<italic>P</italic><0.05）. Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect， No. 1 was superior to No. 2， while in terms of local effect， No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics， while No. 2 had an advantageous effect on intestinal sensation over No. 1.
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The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.
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Animales , Ratas , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Diarrea , Heces , Síndrome del Colon Irritable/tratamiento farmacológico , Privación Materna , Metabolómica , Espectrometría de Masas en Tándem , ValerianaRESUMEN
Introduction: Irritable Bowel Syndrome is a complexinflammatory disease of gastrointestinal tract affectingquality of life and productivity caused by alteration of theintestinal bacteria resulting in disruption of the Gut BrainAxis. Replenishing the gut microbiota with lactic acid bacteria(LAB) delivered through homemade yogurt is used to achieveremission and complete cure for IBS. Present study aimed toevaluate if homemade yogurts as dietary supplement withoutchanging food habits in patients can provide remission andcure for `Irritable Bowel Syndrome (IBS).Material and methods: The background details on occurrenceof IBS was collected on sample population (n=10330) fromIndia in the age group of 45 - 90+ years from different distinctregions. Laboratory studies for strain identification, stabilityand suitability were conducted on yogurt. 150 patientsidentified were then treated with daily dosage of 24ouncesfor a period of 400 days. 189 patients with severe IBS of agegroup 15 yr to 75 yrs in United States were treated followingsame protocol. Placebo studies were conducted on n=17 for aperiod of 400 days where patients were allowed to maintaintheir routine dietary habits.Results: Yogurt has all desired physicochemical andmicrobiological characteristics to be used for treating IBS.91% of the sample population achieved remission within180+/-20 days and 96.4% achieved complete cure within300 days. 98.2% of the population achieved remission andcomplete cure within 400 days in Indian trials. The IBSpatients from the United States (n=189) achieved completecure within 180-200days. (P <.001)Conclusion: Homemade yogurt has all desired probioticcharacteristics and offers remission and complete cure for IBSwithout any side effects if consumed in sufficient quantitieson regular basis.
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Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the common functional gastrointestinal diseases in clinical practice, its pathogenesis is diverse. Because of its sudden and lingering intractable symptoms, it seriously affects patients' work and life. IBS-D patients suffer from repeated illnesses, which often affect their lives with mental symptoms such as anxiety and depression. Anxiety and depression can also affect visceral sensation, increase intestinal sensitivity, aggravated by interaction between physical symptoms and mental symptoms. The main pathogenesis of IBS-D such as visceral hypersensitivity, gastrointestinal motility disorders, intestinal infections, and psychosocial factors are all related to brain-gut interaction disorders. Patients with IBS-D are prone to brain-gut interaction disorders due to long-term chronic mental stress. Brain-gut interaction is the main mode of regulation of gastrointestinal function in the brain-gut axis. Traditional Chinese medicine （TCM） believes that the main syndrome type of IBS-D patients is liver stagnation and spleen deficiency, while liver stagnation will be unsatisfactory, and the secretion and content of various neurotransmitters in the brain are closely related to emotions. Tongxie Yaofang is a commonly basic prescription used for the clinical treatment of IBS-D liver stagnation and spleen deficiency syndrome. It has the functions of softening the liver and replenishing the spleen, removing dampness and stopping diarrhea, and has a significant clinical effect. At present, many animal experiments and clinical studies have explored the mechanism of Tongxie Yaofang in treating IBS-D and its effect on brain-gut interaction function and brain-gut peptide content, but the main liver drainage and brain-gut interaction have not been linked. The author took the correlation between liver liver govers regulating and brain-gut interaction as the starting point, explored the mechanism of Tongxie Yaofang in treating IBS-D based on brain-gut interaction disorder, and explained the correlation between the three. Based on the research literature of Tongxie Yaofang in the past 5 years and the interaction between Tongxie Yaofang and brain-gut interaction, the author explored the effect of Tongxie Yaofang in treating IBS-D by affecting the brain-gut axis and brain-gut peptides.
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Objective:To observe the clinical efficacy of Tongxie Yaofang on irritable bowel syndrome-D (IBS-D) of liver-stagnation and spleen-deficiency type, in order to explore its mechanism in regulating brain-intestine interaction by changing the intestinal flora before and after treatment. Method:Totally 116 patients with IBS-D with liver stagnation and spleen deficiency who were diagnosed from July 2016 to December 2018 were randomly divided into observation group and control group, with 58 patients in each group. Observation group was treated with Tongxie Yaofang orally. Control group was treated with pivalvonium orally. Both groups were treated for 4 weeks. Scores of traditional Chinese medicine pattern curative effect scoring system (TCM-PES), IBS quality of life questionnaire (IBS-QOL), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of two groups were compared before and after treatment. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were detected before and after treatment by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) was used to detect changes in Escherichia coli, Bifidobacteria, Lactobacillus acidophilus and Streptococcus faecalis and other intestinal flora before and after treatment. Result:TCM-PES and IBS-QOL scores of two groups were improved after treatment. TCM-PES and IBS-QOL scores of observation group were higher than those of control group (P<0.05). TCM syndromes of observation group were significantly higher than those of control group (P<0.05). SAS and SDS scores were significantly lower after treatment. SAS and SDS scores of observation group were lower than those of control group after treatment (P<0.05). Plasma CGRP and VIP decreased after treatment. Plasma CGRP and VIP in observation group were significantly lower than those in control group (P<0.05). There was no significant change in E. coli after treatment in two groups. After treatment, L. acidophilus, Bifidobacterium, and S. faecalis increased (P<0.05). In control group, intestinal L. acidophilus increased after treatment (P<0.05). The differences of intestinal L. acidophilus, Bifidobacterium, S. faecalis in two groups were statistically significant (P<0.05). Conclusion:TCM can alleviate clinical symptoms, such as abdominal pain and diarrhea in patients with IBS-D, improve patients' bad mood and improve their quality of life. This may be related to improvement of intestinal flora imbalance, regulation of brain intestinal peptide secretion and reduction of visceral hypersensitivity.
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OBJECTIVE@#To observe the clinical effect of acupuncture at lower- acupoints and front- acupoints combined with (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism.@*METHODS@#A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared.@*RESULTS@#After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (<0.05).@*CONCLUSION@#The acupuncture at lower- acupoints and front- acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.
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Humanos , Puntos de Acupuntura , Terapia por Acupuntura , Ansiedad , Depresión , Diarrea , Medicamentos Herbarios Chinos , Usos Terapéuticos , Síndrome del Colon Irritable , Psicología , Terapéutica , Hígado , Medicina Tradicional China , BazoRESUMEN
Here we used a meta-analysis of several clinical trials to determine whether anti-Helicobacter pylori therapy has any positive effect on IBS patients. Here we compared the effective clinical remission rates between IBS patients treated with anti-H. pylori therapy and those who were not. This data would provide more clinical evidence regarding the efficacy of novel treatments and intervention points for IBS patients. Relevant studies were identified using keyword searches on various electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, CNKI, and CBM. Keywords included "helicobacter pylori" and "irritable bowel syndrome" among others. The literature was screened using relatively strict inclusion and exclusion criteria and RevMan 5.3.5 and Stata 15.1 software were used for meta-analysis and to assess publication bias and sensitivity. A total of ten studies met all of the inclusion criteria; these included 655 IBS patients with H. pylori infection, of these, 385 patients were in the experimental group and 270 patients were in the control group. A random-effects model was used to pool the odds ratios (ORs) with a 95% confidence interval (CIs) and the combined OR was 2.87 (95% CI: 1.74-4.72), p<0.0001. These findings suggest that anti-H. pylori therapy can effectively improve the remission rates of H. pylori-positive IBS patients. H. pylori infection is known to correlate with the incidence of IBS. Anti-H. pylori treatment can effectively improve the clinical remission rates of IBS patients. Whether this means that IBS patients should be actively treated with anti-H. pylori compounds as a novel strategy to improve the remission rates needs to be evaluated in vivo.