Clinical Efficacy And Mechanism Of Ulcerative Colitis "treatment With Carbuncle" Strategy

Objective:Firstly,to summarize Professor Jiang Shumin's academic thought and experience of "treating UC with carbuncle" through theoretical research.Then,through clinical trials,to observe the efficacy and safety of Xiaoyongzhili decoction in the treatment of UC patients with active colonic dampness-heat type.Finally,through animal experiment,to analyze the possible mechanism of effect of Xiaoyongzhili decoction.Materials and Methods:First of all,through theoretical research,to sort out the inheritance of Professor Jiang Shumin's academic thought of "treating UC with carbuncle",to summarize Mr.Jiang's understanding of the causes and pathogenesis of the traditional Chinese medicine of UC,to analyze its treatment characteristics and experience for this disease,and to analyze the compatibility characteristics,formulation principles and prescription efficacy of Xiaoyongzhili decoction.Then,through clinical trials,48 patients with UC who met the inclusion criteria were randomly divided into control group and treatment group.The control group was treated with Mesalazine sustained-release granules,and the treatment group was combined with Xiaoyongzhili granules on this basis.The course of treatment was 2 months.After the course of treatment,the clinical efficacy,TCM syndrome efficacy,TCM main syndrome total score,modified Mayo score,Baron endoscopy score,IBDQ score,blood routine,liver and kidney function and other safety indexes of 2 groups of patients were evaluated.Finally,through animal experiments,51 SD rats were randomly divided into blank group and model group,and the model rats were free to drink 4%DSS solution for 7 days to establish UC rat model.After the success of the building,and then build model rats were randomly divided into model group,anti check flow field soup low,medium and high dose group and willow nitrogen sulfonyl pyridine group,and all the rats lavage treatment for 7 days.The blank group and the model group were irrigated with the same amount of normal saline,and the traditional Chinese medicine group and the western medicine group were irrigated with different concentrations of Xiaoyongzhili decoction and sulfasalazine suspension,respectively.During the experiment,the rats' general state,body weight,stool occult blood and other conditions were observed every day.After the course of treatment,the rats were anesthetized,the samples were collected,the blood was collected from the abdominal aorta,and the colon tissue was separated.Finally,the changes of general state,body weight,colon length and DAI score were observed in each group.The histological morphology was observed and the histological score was evaluated.The contents of IL-1?,IL-6,TNF-? and MPO in serum were detected by ELISA.The phosphorylated ERK,JNK,p38MAPK and NF-?Bp65 proteins in colon tissue were detected by immunohistochemical method,and the average optical density was determined.ERK,JNK,p38MAPK,NF-?Bp65 and phosphorylated proteins in colon tissue were detected by Western blot,and gray scale was determined.Results:The theoretical researchProfessor Jiang Shumin believes that "spleen deficiency is the origin of the disease","dampness and heat,poison and blood stasis" are the key pathological factors of UC,and"carbuncle caused by toxic heat" is the characteristic of the disease,he believed that the pathogenesis of UC was as follows:dampness and heat blocked the intestinal tract,Qi and blood stagnated,extreme heat became toxic,turbidities and toxins bonded to each other in the intestines,and intestinal mucosa formed carbuncle.Professor Jiang Shumin made good use of the towing method in clinical treatment,adopted the treatment principle of "eliminating carbuncle and removing rot",and created "Xiaoyongzhili decoction".The clinical research1.Comparison of clinical efficacy:the total effective rate was 90.9%in the treatment group and 78.3%in the control group,which was higher in the treatment group than in the control group,but there was no statistical difference(P>0.05).2.Comparison of efficacy of TCM syndromes:the total effective rate of the treatment group was higher than that of the control group(P<0.05).3.Comparison of the total scores of major TCM syndromes:Compared with before treatment,the scores of TCM syndromes in both groups were decreased(P<0.05);The scores in treatment group were lower than those in control group(P<0.05).4.Modified Mayo score comparison:Compared with before treatment,Mayo score decreased in both groups(P<0.05);The scores in treatment group were lower than those in control group(P<0.05).5.Comparison of Baron endoscopic scores:Compared with before treatment,Baron endoscopic scores were decreased in both groups(P<0.05);The scores in treatment group were lower than those in control group(P<0.05).6.Comparison of IBDQ scores:After treatment,IBDQ scores in both groups were higher than those before treatment(P<0.05);The scores in treatment group were higher than those in control group(P<0.05).7.Detection of safety indicators:After the course of treatment,blood routine tests,liver and kidney function tests of patients in the two groups were normal,and no adverse reactions occurred in all cases.The experimental research1.Successful replication of UC model? During the modeling period,the occult blood test of rats began to show positive(+)from the 3rd day;From the 4th to 5th day,the body mass gradually decreased and the stool became thin,the stool occult blood test was strongly positive(+++).From day 6-7,there is blood in the stool.? The results of visual and pathological observation of the colon tissue:hyperemia and erosion on the surface of the colonic mucosa were observed by the naked eye,especially at the location 4-6cm away from the anal opening;Pathologically,the mucosal epithelium was obviously damaged,crypt structure disappeared,goblet cells were greatly reduced,and inflammatory cells were infiltrated in the mucosa and submucosa.2.Effect of Xiaoyongzhili decoction on general state change of UC ratsAfter the treatment,the rats in blank group were active,with shiny fur,normal feeding and stool.Compared with the blank group,the fur of the rats in the model group was lack of luster,the food intake decreased,the activity decreased,the spirit was listless,and there was blood mixed in the stool.Compared with model group,the general state of rats was improved to different degrees in each dose of Chinese medicine group and western medicine group.3.Effect of Xiaoyangzhili decoction on the body mass change of UC ratsDuring the experiment,the body weight of the blank group increased gradually andreached the maximum on the 14th day of the experiment.The body weight of the model group gradually decreased from the third day and reached the lowest value on the 14th day of the experiment,which was statistically different from that of the blank group(P<0.01).The body weight of TCM and western medicine groups in the first week decreased to the same degree as that of model group(P>0.05).After the end of the experiment,the body weight of rats in TCM dose groups and western medicine groups was increased compared with that in model group(all P<0.01).4.Effect of Xiaoyongzhili decoction on DAI score of UC ratsCompared with blank group,DAI score in model group was significantly higher(P<0.01);Compared with model group,scores of TCM group and western medicine group were decreased(P<0.05,P<0.01).5.Effect of Xiaoyongzhili decoction on the change of colon length in UC ratsCompared with the blank group,the colon in the model group was significantly shortened(P<0.01);compared with the model group,the colon in each dose of Chinese medicine group and western medicine group was significantly longer(P<0.01).6.Effect of Xiaoyongzhili decoction on histopathological changes in UC rats?Under the microscope:In blank group,the colonic mucosal surface tissue of rats was complete,the crypt structure was normal,and the arrangement was regular.A large number of goblet cells could be seen,and no inflammatory cell infiltration was found.In the model group,the mucosal epithelium was seriously damaged,crypt structure disappeared,goblet cells were greatly reduced,and a large number of inflammatory cells were infiltrated.Compared with the model group,the mucosal epithelium of the high-dose group and the western medicine group was complete,the structure of crypt was regular,goblet cells were significantly increased,and a small amount of inflammatory cells were infiltrated.Mucosal epithelium of medium dose group was more complete,crypt structure was irregular,crypt atrophy and branch were visible,inflammatory cell infiltration was reduced;In the low-dose group,the integrity of mucosal epithelium was slightly improved,the infiltration of inflammatory cells was slightly reduced,and the crypt structure was still damaged obviously.? Histopathological score:Compared with blank group,the score of model group was significantly increased(P<0.01);Compared with model group,all doses of Chinese medicine group and western medicine group were significantly decreased(P<0.05,P<0.01).7.Effects of Xiaoyongzhili decoction on the contents of IL-1?,IL-6,TNF-? and MPO in serum of ratsCompared with blank group,the contents of IL-1?,IL-6,TNF-? and MPO in serum of model group were significantly increased(P<0.01).Compared with model group,the contents of IL-1?,IL-6,TNF-? and MPO in serum of TCM groups and western medicine groups were significantly decreased(P<0.05,P<0.01).8.The levels of phosphorylated ERK,JNK,p38MAPK and NF-? Bp65 in tissues were detected by immunohistochemical method?Results under light microscope:The p-ERK,p-JNK,p-p38MAPK and p-NF-? Bp65 proteins were mainly expressed in cytoplasm,and they were all brown or brown-yellow in colonic mucosa and submucosa.?The p-ERK content:Compared with blank group,it was significantly increased in model group(P<0.01);Compared with model group,each dose of Chinese medicine group and western medicine group was significantly decreased(P<0.05,P<0.01).?The p-JNK content:Compared with blank group,model group was significantly increased(P<0.01);Compared with model group,medium dose group,high dose group and western medicine group were significantly decreased P<0.01),but there was no difference in low dose group(P>0.05).?The p-p38 content:Compared with blank group,model group was significantly increased(P<0.01);Compared with model group,medium dose group,high dose group and western medicine group were significantly decreased(P<0.01),but there was no difference in low dose group(P>0.05);?p-NF-? Bp65 content:Compared with blank group,model group was significantly increased(P<0.01);Compared with model group,all doses of TCM groups and western medicine groups were significantly decreased(all P<0.01);9.Western blot was used to detect ERK,JNK,p38MAPK,NF-?Bp65 and their phosphorylated proteins in rat colon tissueCompared with blank group,the levels of ERK,JNK,p38MAPK,NF-?Bp65 and its phosphorylated protein in colon tissue of rats in model group were significantly increased(P<0.01).Compared with the model group,the levels of ERK,JNK,p38MAPK,NF-?Bp65 and its phosphorylated protein in colon tissue of rats in different TCM groups and western medicine groups were significantly decreased(P<0.05,P<0.01),except that there was no significant difference in p-JNK protein content between the low-dose group and the model group(P>0.05).Conclusion:1.Professor Jiang Shumin "treating UC with carbuncle" has a clear theoretical origin and distinct academic characteristics.He founded "Xiaoyongzhili decoction" to provide a new treatment idea for the clinical treatment of this disease.2.Xiaoyongzhili decoction combined with western medicine compared with western medicine alone,can significantly improve the efficacy of TCM syndromes in patients with mild and moderate colonic dampness-heat type UC at active stage,reduce the total score of main TCM syndromes,improve the main clinical symptoms,reduce endoscopic mucosal score,promote the healing of intestinal mucosal ulcers and improve the quality of life of patients.3.In the clinical trial,the safety indicators of patients did not change,and no adverse reactions occurred.Xiaoyongzhili decoction is safe and effective,with no side effects,and can be promoted in clinical practice.4.Xiaoyongzhili decoction can significantly improve the general state of UC model rats induced by DSS,and inhibit the histopathological damage of colonic mucosa.5.The contents of IL-1?,IL-6,TNF-? inflammatory cytokines and MPO in the serum of UC model rats were significantly increased,and their levels were positively correlated with the severity of the disease.6.By inhibiting the contents of L-1?,IL-6,TNF-? inflammatory cytokines and MPO in serum of UC model rats,Xiaoyongzhili decoction can improve intestinal inflammation and reduce mucosal tissue damage.7.The mechanism of action of Xiaoyongzhili decoction in the treatment of UC model rats may be that it can exert anti-inflammatory effect by inhibiting the activation of MAPK signaling pathway,down-regulating the expression of NF-?B transcription factor,preventing the nuclear transfer of NF-?B,and reducing the transcription and release of pro-inflammatory cytokines.