| Introduction:Functional constipation(FC)is a common disease of digestive system.It is a group of symptoms characterized by reduced defecation frequency,reduced fecal volume,dry stool,and defecation effort without obvious organic lesions.In recent years,the worldwide incidence of functional constipation is about 14%～16%.The prevalence of functional constipation in the general population of China is 6%-10%.Traditional Chinese medicine has obvious advantages in the treatment of functional constipation,such as small side effects and obvious long-term effects.In our previous study,we found that Yiqirunchang Prescription has a good clinical effect on the treatment of qi-deficiency and intestine-dryness functional constipation,and can improve the number and distribution of ICC in constipation rats by upregulating SCF/c-kit signaling pathway,so as to treat constipation.Based on previous studies,this study will further carry out clinical trials and animal experiments to further study the clinical efficacy and mechanism of Yiqirunchang prescription in the treatment of functional constipation.Obj ective:1.A simple randomized controlled trial was conducted to study the clinical efficacy of Yiqirunchang prescription in the treatment of functional constipation.2.Further study the effect and mechanism of Yiqirunchang Prescription on functional constipation through rat animal experiment.Methods:1.Clinical trial:In this study,patients meeting the standards of intake and discharge were randomly divided into Yiqirunchang Prescription group in the treatment group and Qirongrunchang oral liquid group in the control group,and received oral drug therapy for 4 weeks.The TCM symptom score table,Bristol stool type,Wexner Constipation Score Sheet and The Quality of life scale for constipation patients(PAC-QOL)were filled in for patients in the two groups at the time of enrollment,2 weeks after treatment,4 weeks after treatment,4 weeks after treatment and 8 weeks after treatment,respectively,to observe the efficacy and long-term efficacy of Yiqirunchang Prescription.Before and after treatment,blood routine examination(RBC,WBC,HGB,PLT),liver function(ALT,AST),kidney function(BUN,Cr)and electrocardiogram were performed in 2 groups,and the occurrence of adverse events during the trial was recorded to evaluate the safety of Yiqirunchang Prescription.2.Animal Experiments:60 healthy male SD rats were randomly divided into blank group and 10,module,50,made module with 12 mg/kg/d loperamide lavage on functional constipation building,3 days after the success of the building to build module 50 rats were randomly divided into model group,control group,high dose treatment groups,dose group,low dose treatment groups in each group 10.The above five groups received 6mg/kg/d loperamide modeling maintenance at 9 a.m.,the control group was given Qirongrunchang oral liquid at 3 p.m.,and the three treatment groups were given different concentrations of Yiqirunchang solution for 7 days of intragastric treatment.After 7 days,the basic conditions and intestinal end-of-carbon propulsion rate of rats in six groups were measured.HE staining was used to observe the morphological changes of colon.The quantity and distribution of c-kit were observed by immunohistochemistry.qPCR was used to detect the mRNA expression of VIP-cAMP-PKA-AQP3 signaling pathway.Western blot was used to detect the expression of PI3K-AKT-mTOR signaling pathway and related proteins.Results:1.Clinical trials:(1)There were 40 cases in the treatment group and 41 cases in the control group who completed the test.The baseline levels of patients in the two groups were basically the same with no statistical difference.(2)During the treatment,in terms of clinical effective rate and TCM syndrome effective rate,the total clinical effective rate of the treatment group was 82.50%and the control group was 53.66%after 2 weeks of treatment,and the total clinical effective rate of the two groups was 92.50%and 80.49%respectively after 4 weeks of treatment.After 2 weeks of treatment,the total effective rate of TCM syndrome in the treatment group and the control group were 87.5%and 63.42%,respectively;after 4 weeks of treatment,the total effective rate of TCM syndrome in the two groups were 97.50%and 87.80%,respectively.In the whole treatment period,the clinical effective rate and TCM syndrome effective rate of the treatment group were better than those of the control group.(3)Comparison of TCM symptom table during treatment:at 2 weeks and 4 weeks,the effect of the treatment group was better than that of the control group,P<0.01.(4)Bristol score during treatment:at 2 and 4 weeks of treatment,the score of the treatment group was closer to that of the normal population,with significant statistical differences compared with the control group(P<0.01).(5)Wexner constipation rating scale during treatment:the treatment group was significantly better than the control group at 2 weeks after treatment in terms of "number of defecation","difficult:painful defecation","Defecation time:squatting time for each defecation(min)" and "failed defecation:the number of unsuccessful defecation every 24 hours",P<0.05.After 4 weeks of treatment,the treatment group also showed a.significant advantage in improving "empty-incomplete empty-feeling" compared with the control group,P<0.05.(6)Comparison of the quality of life scale(PAC-QOL)of constipation patients during treatment:after 2 weeks of treatment,the effect of "somatic symptoms" and "satisfaction" in the treatment group was better than that in the control group,P<0.05.After 4 weeks of treatment,the treatment advantage of the treatment group was further expanded,and there were still statistical differences in "somatic symptoms" and "satisfaction" between the two groups,with P<0.01 and P<0.05,respectively.(7)Comparison of recurrence rates between the two groups:at 4 weeks after treatment,the recurrence rates of the treatment group and the control group were 22.50%and 43.90%respectively;at 8 weeks after treatment,the recurrence rates of the two groups were 35.00%and 58.54%respectively.The recurrence rate in the treatment group was lower than that in the control group during the whole follow-up period.(8)Comparison of TCM symptom table during the follow-up period:all indexes in the treatment group were superior to the control group at 4 weeks after the treatment except"dry and hard stool",with statistical difference(P<0.05).At 8 weeks after treatment,all indexes in the treatment group were better than those in the control group,P<0.05.(9)Comparison of Bristol score during follow-up:there was no statistical difference between the two groups at 4 weeks after treatment,but the effect of the treatment group was better than that of the control group.At 8 weeks after treatment,the effect of the treatment group was better than that of the control group,P<0.05.(10)Wexner scale comparison during the follow-up period:4 weeks after the treatment,the treatment group was superior to the control group in terms of indicators of "difficulty:painful defecation","emptation:incomplete emptation" and "defecation failure:the number of unsuccessful defecation every 24 hours",P<0.05.8 weeks after the treatment,there were significant differences between the treatment group and the control group in the indicators of "difficulty:painful defecation","defecation time:squatting time for each defecation(min)","defecation failure:the number of unsuccessful defecation every 24 hours",P<0.01.(11)Comparison of quality of life scale(PAC-QOL)for constipation patients during follow-up:at 4 weeks and 8 weeks after treatment,the long-term efficacy of "somatic symptoms" and "satisfaction" in the treatment group was better than that in the control group,P<0.05.(12)Safety evaluation:Blood routine(RBC,WBC,HGB,PLT),liver function(ALT,AST),kidney function(BUN,Cr)and ELECTROcardiogram were all within the normal range before and after treatment in both groups,and no adverse events occurred.2.Animal Experiments:(1)Comparison of basic conditions of rats in each group:Weight gain in rats on 24 h,24 h waste grain number,feces moisture content and the intestinal propulsion rate at the end of the carbon,in the comparison of the change trend of three indicators have consistency,all is the worst model group effect,compared with the blank group(P<0.05,the three drugs found in the comparison of the intervention group were best is dose in the treatment group effect,treatment of low dose group of times,and then the control group,Finally,there were statistical differences in pairwise comparison for the high-dose group.(2)Comparison of histomorphological conditions of rats in each group:In HE staining,a large number of inflammatory cell infiltrates were observed under the microscope of the model group,and the glands were not arranged neatly and compact,which was more obvious under high magnification microscope.Compared with the model group,the drug intervention groups were significantly improved.In immunohistochemical observation,it was found that the model group had obvious differences in c-kit coloring and discontinuous distribution compared with the blank group.Compared with model group,all drug treatment groups showed different degree of improvement.AOD numerical analysis showed that the number of c-kit in each drug intervention group was in descending order from high to high:medium-dose group,low-dose group,control group and high-dose group.The therapeutic effect of the high-dose group was slightly lower than that of the control group,with no statistical difference(P>0.05).The therapeutic effect of medium dose group and low dose group was significantly better than that of control group,both had P<0.01.(3)Comparison of protein expressions related to PI3K-AKT-mTOR pathway in each group:In the PI3K-AKT-mTOR signaling pathway,AKT and mTOR play their roles through the phosphorylation of their proteins,that is,through PI3K-p-AKT-p-mTOR.The changes in the expression of PI3K,p-AKT and p-mTOR proteins in each group were consistent,as follows:Compared with the blank group,the expression of PI3K,p-AKT and p-mTOR proteins in model group was high,P<0.05.Compared with the model group,the four drug intervention groups had different degree of inhibition,P<0.05.The inhibitory effect of medium dose group and low dose group was significantly better than that of control group,P<0.05,and the effect of high dose group was inferior to that of control group.(4)Comparison of VIP-cAMP-PKA-AQP3 pathway-related mRNA expression in rats of all groups:the change trend of VIP mRNA,cAMP mRNA,PKA mRNA and AQP3 mRNA in rats of all groups was consistent,which were as follows:Compared with the blank group,the model group was lower,P<0.05,and the four drug intervention groups were higher than the model group.Comparison between the four groups,treatment of medium dose group,treatment of low dose group were significantly better than the control group,P<0.05,treatment of high dose group was inferior to the control group.Conclusion:1.Clinical trials:Clinical observation shows that Yiqirunchang Prescription has good clinical efficacy in the treatment of functional constipation syndrome of qi deficiency and dryness of intestine.It also shows good long-term efficacy 4 weeks and 8 weeks after the end of treatment,and no adverse events occur,indicating that Yiqirunchang Prescription has good clinical safety.2.Animal Experiments:Experimental studies have shown that Yiqirunchang Prescription has significant therapeutic effect on functional constipation,and the mechanism may be related to the down-regulation of PI3K-AKT-mTOR signaling pathway to increase the number of ICC to promote intestinal movement and up-regulation of VIP-cAMP-PKA signaling pathway to increase AQP3 mRNA expression to increase fecal water content. |
PDF Full Text Request