The Clinical Study Of Sansheng Tongbian Decoction In The Treatment Of Functional Constipation (excess Heat Of The Intestine) And The Experimental Study Of The Laxative Effect And Mechanism Of Peon

Part Ⅰ:A Randomized,Double-blind,Placebo-controlled clinical study of Sanshengtongbian decoction in Treating Functional Constipation with Intestinal Excess Heat SyndromeObjective:To evaluate the clinical effect of Sanshengtongbian decoction on intestinal excess heat syndrome of functional constipation and its impact on quality of life.Methods:70 cases of functional constipation with TCM syndrome of intestinal excess-heat were randomly divided into the treatment group and the placebo group,35 cases in each group.The patients were treated with Sanshengtongbian decoction or placebo for 4 weeks respectively.The primary outcomes were the effective rate of western medicine symptoms and the effective rate of TCM symptoms.The secondary outcomes were the total score of western medicine symptoms,the total score of TCM symptoms,the single symptom degree of western medicine,the single symptom degree of TCM and quality of life score.Result:After 4 weeks of treatment,for the treatment group,the effective rates of western medicine symptoms of FAS analysis and PPS analysis were 74.29% and 78.79% respectively.For the placebo group,the effective rates of western medicine symptoms of FAS anaylsis and PPS analysis were 45.1% and 48.48% respectively.There were significantly statistical differences between the two groups(P<0.01).The total score of western medicine symptoms in both the treatment group and the placebo group at 4 weeks were significantly lower than those before treatment and after 2 weeks treatment(P<0.05).The total score of western medicine symptoms of the treatment group at 4 weeks was significantly lower than that in the placebo group(P<0.05).For the treatment group,the effective rates of TCM symptoms of FAS analysis and PPS analysis were 77.14% and 81.82% respectively.For the placebo group,the effective rates of TCM symptoms of FAS anaylsis and PPS analysis were 37.14% and 36.36% respectively.There were significantly statistical differences between the two groups(P<0.01).The total scores of TCM symptoms in both the treatment group and the placebo group at 4 weeks were significantly lower than those before treatment and after 2 weeks treatment(P<0.01).The total score of TCM symptoms in the treatment group at 4 weeks was significantly lower than that in the placebo group(P<0.05).In the comparison of single symptom degree of western medicine between the treatment group and the placebo group,in FAS anaylsis,except for defecation frequency,Bristol stool form scale,excessive defecation and defecation difficulty,tenesmus /incomplete defecation/distension,abdominal distension and defecation time of the treatment group were all superior to those of the placebo group(P<0.05).In PPS analysis,all single symptom degrees of western medicine in the treatment group were superior to those in the placebo group(P<0.05).Compared with the placebo group,in both FAS anaylsis and PPS analysis,the degrees of dry stool and abdominal distention/pain in the treatment group were significantly lower(P<0.05).The scores of life quality of the treatment group in both FAS analysis and PPS anaylsis were improved significantly(P<0.01)and significantly lower than those in the placebo group(P<0.05).The incidences of adverse events in the treatment group and the placebo group were 2.86% and 5.71% respectively(P>0.05).Conclusion:Sanshengtongbian decoction could effectively and safely improve the constipation symptoms of both western medicine and TCM syndrome and quality of life in patients of functional constipation with intestinal heat-excess syndrome.Part Ⅱ:Experimental study on the effect and the mechanisms of paeony on constipation model ratsObjective:To compare the laxative effect of different varieties,processing methods and doses of paeony on rats with chronic functional constipation for optimizing the formula of Sanshengtongbian decoction,and to explore its possible mechanism from gastrointestinal hormones,aquaporins and chloride channels.Methods:Constipation rat model was established by intragastric administration of compound diphenoxylate.The constipation model rats were respectively treated with high-dose raw red peony/raw white peony,high-dose raw red peony/ fried red peony,and low,medium and high-dose raw red peony.The laxative effects of peony were evaluated with the number,the weight and the water content of the rat feces.Western Blot was used to determine the expression of chloride channels CFTR and CLC-2 in colonic tissue of constipation model rats,and ELISA was used to meausre the expressions of MTL,GAS,CCK,VIP,5-HT,PP,PYY and AQP4 in colonic tissues.Result:(1)High dose of raw red paeony could significantly increase the number and the weight and the water content of the rat feces(P<0.05).High dose of raw white paeony and high dose of fried red peony and medium dose of raw red paeony could only significantly increase the water content of the rat feces(P<0.05).Low dose of raw red paeony had no effect on the number,the weight and the water content of the rat feces(P>0.05).(2)CLC-2 protein expression in high-dose raw red paeony group was significantly higher than that of constipation model control group(P<0.05).The expression level of PP was significantly higher while the expression levels of VIP and PYY were significantly lower in the high-dose raw red paeony group than in constipation model control group(P<0.05).The expression level of AQP4 in colonic tissues in high-dose raw red peony group was singificantly decreased compared with the constipation model control group(P<0.01).Conclusion:The laxative effects of paeony on the constipation model rats depended on the varieties,the processing methods and the dosages of paeony.The laxative effect of raw red paeony was stronger than that of white paeony and fried red paeony,and which was dose-dependent.Therefore,it was comparatively reasonable to choose raw red paeony for Sanshengtongbian decoction.Paeony might relieve constipation by acclerating colonic movement through increasing the expression of gastrointestinal hormone PP and inhibiting the expression of VIP and PYY,and increasing intestinal secretion through promoting the expression of chloride channel protein CLC-2 and decreasing the expression of aquaporin AQP4.