Study On The Brain-guit Peptide And SCF/c-kit Signaling Pathway Of Diarrhea-predominant Irritable Bowel Syndrome By Xi-feng-hua-shi Formula

Diarrhea-predominant irritable bowel syndrome(IBS-D)is one of functional gastrointestinal disease.The etiology and pathogenesis are complicated.IBS-D is very difficult to cure.Xi-Feng-Hua-Shi(XFHS)formula is an effective formula of professor Tian Yaozhou,who is the doctoral supervisor of Nanjing University of Chinese Medicine.XFHS formula has the efficacy of soften the liver and extinguish the wind.It is used in treating IBS-D and the therapeutic effectiveness is definitive.But the mechanism has not been fully elucidated.Part I:Theoretical StudyThe current situation of pathogenesis,diagnosis and treatment principles were reviewed basing nmodern medicine firstly.Western medicine just improves symptoms mostly,there is poor efficacy,long-term use of side effects,stop the drug easily rebound and so on.More and more researches show advantages of Chinese medicine in improving symptoms and life quality of patients.In our opinion,Chinese medicine or integrative therapy may be one of the important methods of IBS treatment in the future.Part II:Clinical Research(Clinical study on the effect of XFHS Formula onDiarrhea-predominant Irritable Bowel Syndrome)Objective:To observe the efficacy of XFHS formula on IBS-D patients,And the effect of XFHS formula on brain-gut peptides in the patients with IBS-D.Methods:80 patients who met the diagnostic criteria and inclusion criteria for IBS-D patients were randomly divided into the test group and the control group.The test group was treated with XFHS formula and the control group was treated with pinaverium for 4 weeks.The main TCM clinical symptoms,self-rating anxiety scale(SAS),self-rating depression scale(SDS)scores and the level of vasoactive intestinal peptide(VIP),nerve peptide Y(NPY)in serum were recorded before and after treatument.Results:The total effective rate in test group was 90.4%,which was significantly better than 76.6%of the control group(P<0.05).The TCM clinical symptoms,SAS and SDS scores of the two groups were significantly improved than that of before(P<0.05).While the improvement of symptonms including diarrhea after abdominal pain,irritability,anxiety and depression in the test group was better than the control group(P<0.05).The level of VIP in serun of the two groups were significantly lower than that of before(P<0.05),and the level of NPY in serum of the t&wo groups were significantly higher than that of before(P<0.05),but there was no significant difference between groups(P>0.05).Conclusions:XFHS formula has a significant effect in treating IBS-D.And XFHS formula can regulate the expression of VIP and NPY in the serum of IBS-D patients.Part Ⅲ:Experimental Study(Study on the protective mechanism of XFHS Formula on Diarrhea-predominant Irritable Bowel Syndrome based on SCF/c-Kit signaling pathway)Objective:To observe the curative effect of XFHS formula on IBS-D rats,And the effect of XFHS formula on SCF/c-Kit signaling pathway and brain-gut peptides in the rats with IBS-D.Methods:Wistar rats were divided into control group,IBS-D model group,low dosage XFHS group,high dosage XFHS group and western medicine group randomly.The model was induced by separation of breast milk + coloclysis of acetic acid.Low,high dosage XFHS group and western medicine group rats were given by gavage with Low,high concentration XFHS formula and pinaverium respectively.And equal amount of normal saline was admnistrated by gavage in the normal group and model group.Two weeks later,the loose stools rate,abdominal withdrawal reflex(AWR)and abdominal myoelectric activity were recorded,the level of VIP,NPY in serum were detected by ELISA,the level of VIP,NPY proteins in the colonic and hypothalamus tissue,level of SCF、c-kit proteins in the colonic tissue were detected by western blot,the level of VIP in serum,the level of SCF、c-kit mRNA in the colonic tissue detected by qPCR.Results:Compared with normal group,the loose stools rate,grades of AWR and abdominal myoelectric activity in the IBS-D model group were significantly lower(P<0.05).After XFHS formula and pinaverium treatment,compared with the IBS-D model group,the loose stools rate,grades of AWR and abdominal myoelectric activity in the XFHS and western medicine group were significantly higher(P<0.05).the level of VIP in serum,colonic and hypothalamus tissue were significantly lower(P<0.05),the level of NPY in serum,the colonic and hypothalamus tissue were significantly higher(P<0.05),and the level of SCF、c-kit proteins and mRNA in the colonic tissue were significantly lower(P<0.05).Conclusions:XFHS formula can reduce the loose stools rate and visceral hypersensitivity by regulating the expression of SCF/c-Kit signaling pathway and brain-gut peptides.