The Effect Of Tiaogan Spleen Method On IBS-D Randomized Controlled Trial And The Effect Of NGF And Its Receptor Expression In Rat Colon Tissue

The paper is divided into two parts:clinical trials and animal experiments.(I)The Clinical Trial:The trial used Chinese medicine to regulate the liver and spleen to intervene the patients with diarrhea-predominant irritable bowel syndrome(IBS-D),compared with the western medicine positive control drug Pinaverium Bromide,to analyze whether there were statistical differences in the overall efficacy,main symptoms,quality of life,etc.between the observation groups,and to make a brief evaluation of drug safety.Clinical studies can be divided into three phases,which are the testing period,intervention period and follow-up period.According to the chronological order of observing the efficacy indicators,it was divided into 6 observation points.A total of 108 subjects entered the randomized trial,103 completed the trial(97.2%),and none of the subjects terminated the trial due to serious adverse reactions.All subjects entered the complete analysis set(FAS)for overall efficacy analysis,105 subjects entered the safety analysis set(SAF)for drug safety analysis,and the final test completed 98 cases into the per-protocol set(PPS)for comparative analysis of each efficacy index.For the demographic characteristics and baseline conditions of the PPS subjects,continuous variable descriptions were described using means(standard deviations)and composition ratios were described using the number of cases(percentage).Age(years)[C:49.7(12.1),T:45.1(12.5)](C:control group;T:experimental group,the same below),gender(male)[C:32(65.3),T:33(67.3)],course of disease(years)[C:5.7(5.0),T:5.4(4.3)],body mass index(kg/m2)[C:23.1(3.8),T:23.9(3.9)],and groups were treated as dependent variables to establish a general linear regression model for each of the efficacy indicators.IBS-SSS,TCM Syndrome Scale scores,abdominal pain scores,diarrhea frequency scores,stool trait Bristol scores,and IBS-QOL were used as efficacy indicators in PPS subjects.Their values were all estimated by the general linear regression model in order to control baseline differences and produce a set of estimates used to evaluate efficacy indicators.The efficacy indicators were used to statistically estimate the difference between the observation points 1,2,3,4,and 5 and the observation point 0(the degree of each efficacy index deviating from the baseline)and the difference between the corresponding observation points.Observed indicators are continuous variables,and the statistics of each index are described with the mean and 95%confidence intervals.The results of the study showed that the IBS symptoms(abdominal pain,frequency of diarrhea,and stool traits)during the four-week intervention period were generally better than the Pinaverium Bromide intervention group.Observed at point 2 can see significant differences between groups(P<0.01).At the 3rd,4th,and 5th observation points in the follow-up period,the improvement of the symptoms in the same group was not significantly different from the observation point 2(P>0.05),and no rapid fall trend was observed.There was no significant difference in the degree of diarrhea among the groups(P>0.05).There were significant differences between the other groups(P<0.01).The improvement of individual symptoms showed different characteristics.The intervention of regulating Liver and Spleen-invigorating the spleen had a satisfactory effect in relieving the symptoms of abdominal pain,and the average degree improved to normal(degree of 0)in 5 grades,and achieved statistical difference compared with the control group’s intervention in 2 levels(P<0.01),which were 2.5 times the improvement level of the control group.During the follow-up period,the degree of abdominal pain relief was stable,and the average level was similar to the observation point 2 level(P>0.05).The degree of improvement in the degree of diarrhea is not ideal.Although the improvement during the intervention period was better in the experimental group than in the control group(P<0.01)and the degree of improvement continued to improve during the follow-up period(comparison between the groups P>0.05),but the degree of improvement has not yet reached a level(One point average is 1 point),so the overall improvement is not satisfactory.In the comprehensive evaluation of symptoms of IBS symptoms SSS scale and TCM syndrome scale,two evaluation indicators of observation point 2 in the intervention period and observation point 5 in the follow-up period showed that the experimental group was significantly more effective than the control group(P<0.01)in teh PPS subjects.The SSS scale is more likely to meet the clinical recovery standard than the TCM syndrome scale in the FAS subjects.The satisfaction of PPS subjects with the quality of life in the Tiaoganlipi group was higher than that in the control group(P<0.01),and the degree of difference was relatively stable.Subject vital signs,important laboratory tests,and colonoscopy did not show any significant abnormalities after this observation period or intervention period.The incidence of adverse events in the trial group was lower than that in the control group(17%and 28.8%,respectively),and adverse events were mostly mild.No subjects stopped intervention because of obvious adverse effects.Most of the most common adverse events were disorders of the digestive tract,infections,etc.No serious side-effects associated with the central nervous system were found.No deaths were reported and safety was acceptable.This study did not discuss the recurrence of the subjects.The main reason is that there is no clear and uniform description of the recurrence judgment index in the clinic.In addition,the symptom performance and satisfaction with the quality of life of the subjects during the follow-up period are relatively stable.Even if there was a drop in the mean value,the 95%CI was not statistically different from the other observation points,the influence of random errors could not be ruled out.Therefore,the recurrence situation was not discussed.In general,the effect of Tiaoganlipi is better than that of the positive drug Pinaverium Bromide.The therapeutic effect of Tiaoganlipi prescription is stable and safe at the follow-up period.It can be popularized in clinic.The frequency of diarrhea can be increased or decreased under the premise of safety on the basis of the original prescription.To achieve satisfactory clinical results requires other clinical trials to demonstrate.(II)The Animal experiment:To investigate and analysis the effects of Shuganjianpi prescription(SGJP)on the expression of nerve growth factor(NGF),Trk A receptor and P75 receptor of colon mucosa in the irritable bowel syndrome-diarrhea predominant(IBS-D)model rats.Eighteen 2-day-old male Sprague-Dawley(SD)rats were randomly divided into three groups:a normal group,a model group,a SGJP group.All groups except the normal group received neonatal maternal separation plus restraint stress for preparation of IBS-D model,which were intragastric administrated with saline and SGJP for 14 days respectively after modeling successfully.The colon mucosa of rats was taken for detecting the expression of NGF,Trk A receptor and P75 receptor by enzyme linked immunosorbent assay.The SGJP reduced the expression of NGF(P>0.05),TrkA receptor(P<0.05)and P75(P<0.05)receptor of colon mucosa in IBS-D rats.The partial mechanisms of improving the visceral sensation and diarrhea with SGJP in IBS-D rats might be realized through regulating NGF and its receptors.