Clinical And Experimental Studies On The Treatment Of Active Ulcerative Colitis By Removing Heat And Dispersing Dampness

Objective and Significance:The incidence of ulcerative colitis(UC) has been steadily increased in China since last decades.UC has been considered as precancerous lesions of colon cancers and classified as one of refractory diseases in modern society by World Health Organization.The etiology and pathogenesis of UC have not been fully elucidated,so there is no radical treatment for UC.Treatment of UC by western medicine has some shortcomings,such as unsatisfied efficacy and considerable side effects,which reduce patients' compliance.Therefore, it urgently needs to find alternative treatments with significant clinical improvement and little adverse effects.Based on the results from large amounts of previous clinical and experimental studies,we propose the pathogenesis of UC from the Chinese traditional medicine point of view.The characteristic of active UC is mainly wetness-heat of large intestine while that of remission stage is largely deficiency of spleen-Qi and stomach-Qi.Treatment for the former is dependent on removing heat and dispersing dampness but treatment for the latter should strengthen the spleen and replenish Qi.Both acute and remission stages of UC have Qi-stagnancy and blood stasis.Chinese traditional medicines were applied to treat patients with mind and moderate UC which can reflect on their characteristics and advantages.Patients with UC at acute stage were treated with a combination of oral Changyanging 1 and enema Changdiging fluid.Both Changyanging 1 and Changdiging fluid have been used in TCM hospital of Guangdong province for more than 10 years.Recent studies have demonstrated that oxygen-free radicals play a role in the pathogenesis of UC.To explore the therapeutic effects and mechanisms, we measured the effect of removing heat and dispersing dampness(treatment by combination of oral Changyanging 1 and enema Changdiging fluid) on colon mucosa damage index(CMDI),the dynamic changes of superoxide dismutase(SOD) activity and MDA level in serum and colon tissues of rats with experimental ulcerative colitis.By means of randomized controlled prospective clinical study,we also evaluated the clinical efficacy and safety of the combination of Changyanqing 1 and Changdiqing fluid in the treatment of UC.Results from these studies,we could demonstrate their effectiveness on the treatment of UC and facilitate their clinical application.Methods:This thesis included two parts:experiment study and clinical study.Methods of experimental study:8 rats were randomly selected as the normal group from 51 healthy female Sprague-Dawley(SD) rats.Active UC was induced by trinitro-benzene-sulfonic acid(WNBS) and ethanol solution in 43 rats.Three days after establishing the model of UC,2 rats randomly selected were dissected in order to observe the success of model.The remainders(41 rats) were randomly divided into three model groups,i.e.,Changdiqing group, Changdiqing + Changyanqing group and salicylazosulfapyridine(SASP) group.Four days after establishing the model of UC,the rats in both normal and model groups were treated with normal Saline enema(NSE).Rats in the other 3 groups were treated with Changdiqing enema,Changdiqing enema plus Changyanqing garage,and SASP by gavage and enema,respectively.The protection mechanism of the method of removing heat and dispersing dampness was observed in terms of general condition,weight,CMDI,dynamic changes of SOD activity and MDA level in serum and tissues of colon.The course of treatment was 2 weeks.Methods of clinical study:Seventy patients fulfilling the inclusion criteria were randomly divided into two groups.Thirty-five cases in experimental group were treated with the combination of oral Changyanqing 1 and enema Changdiqing fluid,while 35 cases in control group were treated with SASP by oral administration and enema.The clinical efficacies were evaluated by observing patients with clinical symptoms and signs(including diarrhea, mucous bloody stool,rectal tenesmus,etc.),the characteristics of tongue and pulse,by measuring ESR and CRP,and by detecting fecal occult blood and colon mucous.The course of treatment was 4 weeks.Results:1 The results of experimental study: 1.1 The improvement of general conditions in rats:Two days after establishing the model of UC,all rats had loose stools,followed by mucous stool and bloody purulent stool.Rats in model group were companied with slow response,lack of movement,tiredness,messy hair,hollow back,poor appetite and little drinking-water,lose weight,and even death.One week after medication,mucous bloody stool gradually reduced while physical activities gradually improved. Both diet-uptake and drinking-water were gradually increased in the rats of other three treatment groups.The improvement of symptoms was most significant in Changdiqing + Changyanqing group.1.2 Weight changes in rats:The weight of rats had rapid growth in Changdiqing group and Changdiqing + Changyanqing group,but there was no significant difference in weight change between these groups(P＞0.05).Comparing Changdiqing group with SASP group,a significant difference in weight change was noted(P＜0.01).Comparing Changdiqing + Changyanqing group with SASP group, the difference in weight change was also statistically significant (P＜0.01).Comparing SASP group with model group,no significant difference in weight change was found(P＞0.05).Rats grew slower in SASP group.1.3 CMDI changes in rats:CMDI was highest in model group,compared with normal group,the difference was statistically significant(P＜0.01).After treatment,CMDI declined in 3 treatment groups.Comparing the 3 treatment groups with model group,the differences were statistically significant (P＜0.01).Comparing Changdiqing + Changyanqing group with Changdiqing group and SASP group,the differences were statistically significant (P＜0.01).Comparing Changdiqing group with SASP group,no significant difference in CMDI was noted(P＞0.05).1.4 Dynamic changes of SOD activity in rats serum and tissues of colon:Normal group had highest SOD activity,followed by Changdiqing + Changyanqing group, Changdiqing group,SASP group,and untreated model group.The increase of SOD activity was the most remarkable in Changdiqing + Changyanqing group,compared with the other 3 groups,the difference was statistically significant(P＜0.01).1.5 Dynamic changes of MDA level in rats serum and tissues of colon:Dynamic changes of MDA level was as follows:model group＞SASP group＞Changdiqing group＞Changdiqing + Changyanqing group＞normal group.The decline of MDA level was the most notable in Changdiqing + Changyanqing group,compared with the other 3 groups,the differences were statistically significant(P＜0.05 or P＜0.01).2 The results of clinical study:2.1 The result of ESR,CRP:Twenty-one patients in treat group completed the measurements of ESR and CRP after treatment,while 22 patients in control group did.After treatment,both ESR and CRP were decreased when compared to those before treatment(P＜0.05 and P＜0.01 for ESR and CRP,respectively).ESR was significantly low in treated groups if compared to that in control group (P＜0.05).However,CRP had no significant change between treated and control groups.2.2 The detection of fecal occult blood showed that the treat group was superior to the control group(P＜0.05).2.3 Scoring for major symptoms:In treated group all symptoms have improved, compared to those before treatment,the differences were statistically significant(P＜0.05 or P＜0.01) In control group,in addition to rectum searing heat and short red urine,the improvement of other 6 symptoms were compared with before treatment,the difference was statistically significant (P＜0.05 or P＜0.01).After treatment,the improvement of rectal tenesmus and short red urine,the treat group was superior to the control group(P＜0.01).The improvement of other 6 symptoms,comparing the two groups,the difference was not statistically significant(P＞0.05).2.4 Syndromes judged by Chinese traditional medicine standards:In treated group,among the 31 cases,7 cases were cured,lO cases were markedly effective, 12 cases were effective and 2 cases were ineffective,the total effective rate was 92.5%.As for control group,among the 30 cases,2 cases were cured, 5 cases were markedly effective,14 cases were effective and 9 cases were ineffective,the total effective rate was 70.0%.The treat group was superior to the control group in term of Chinese medicine syndromes efficacy(P＜0.05).2.5 The result of examining colon mucosal lesions:Fifteen patients in treat group received colonoscopy after treatment,while18 patients in control group did.Pathologic examination showed that colon mucosal lesions in the treated group improved better than that in the control group(P＜0.05).2.6 The result of clinical comprehensive efficacy:In treated group,among the 31 cases,6 cases were cured,9 cases were markedly effective,12 cases were effective and 4 cases were ineffective,the total effective rate was 87.1%.As for control group,among the 30 cases,3 cases were cured,4 cases were markedly effective,15 cases were effective and 8 cases were ineffective, the total effective rate was 73.3%.The treated group was superior to control group in term of effectiveness on clinical outcome(P＜0.05).2.7 The correlation analysis of clinical comprehensive efficacy and the extent of disease,the severity of disease:There was no correlation between clinical comprehensive efficacy and the extent of disease(P＞0.05).Clinical comprehensive efficacy was negatively correlated with the severity of disease(P＜0.01),the more simple the disease is,the more effective the treatment is.2.8 The result of adverse reactions:During treatment the treated group had no obvious side effects,while one cases in control group occurred leukopenia, and western medicine was suspended after one course of treatment,no special treatment was given.Conclusions:Animal experiments have shown that:the combination of Changdiqing and Changyanqing can significantly relief symptoms such as diarrhea and hematochezia,reduce the ulcer index of colonic mucosa,improve the pathomorphology,increase SOD activity in serum and tissues of colon,and decrease the level of MDA in rats with experimental UC.Clinical study results have shown that:the method of removing heat and dispersing dampness in treating active mild and moderate UC belonging to wetness-heat of large intestine had significant clinical modifications with decrease of ESR,disappearance of fecal occult blood and improvements of cardinal symptom and colon mucosal lesions.The treated group was superior to the control group in term of measurements by Chinese medicine syndromes efficacy and clinical comprehensive efficacy.Results from this study have demonstrated that Changyanqing and Changdiqing combination therapy in treating UC can modify inflammatory inflammation,enhance the protective effect on mucosa cells and promote ulcer healing,through the mechanisms of increasing SOD activity and decreasing MDA level in serum and tissues of the colon.