Yiqihuoxuejiedu method of anti-inflammatory and repair mechanisms of the anti-ulcer colitis recurrence
|School||Beijing University of Traditional Chinese Medicine|
|Course||Chinese medical science|
|Keywords||Resisting relapse Ulcerative colitis Determination of treatment based on differentiation of syndromes Formula of Kuijiefufa Mechanism of action Cytokine|
ObjectiveUlcerative colitis (chronic nonspecific ulcerative colitis) is a disease of digestive tract characterised by chronic inflammation and ulceration of colonic mucous membrane. Clinical manifestation: mucus, pus and blood stool;diarrhea; abdominal pain; tenesmus and so on. It has anfractousive pathogenesy, which they affect each other and even emerge vicious cycle. It causes UC easily to relapse and last a very long period. At present, aminosalicylic acid, cortex steroid hormone and immunomodulator is the effective western medicine. In active stage of ulcerative colitis,these medicine can quickly control the symptoms.The clinical remission rate is high.But the disease is easily recur after drug withdrawal.And side reaction is multi with long-term medication, which causes very low compliance.Professor Wang Xinyue, my tutor who studies UC based on the theory of Traditional Chinese Medicine and Modern Medicine, expound it accurately. Kuijiefufafang is my tutor’s proved recipe based on treating with profiting Qi, promoting blood flow and detoxifying Du. The topic evaluate its therapeutic and resisting relapse effect. It meanwhile investigates the mechanism of resisting relapse effect from the view of restraining the reaction of inflammatory injury, promoting the repair of colonic mucous membrane combining with animal experiment. We deeply analyze the mechanism of repressing recur after henosis in order to offer the objective evidence of reasonably selecting the treating method and medicine.MethodsThe CR study was strictly designed under correlated standard. In combination with actual clinical situation, adopting random positive control method, on the basis of diagnosis criterion established on Inflammatory Bowel Disease Seminar at chengdu in 2000, 85 case of chronic recurrent type in UC active phase and chronic K/o type was selected from out-patient clinic (OPD) and ward of Dongzhimen Hospital, 301 Hospital, 306 Hospital, treated group received tutor’s proved recipe (parching excrementum pteropi 10g, raw pollen typhae 10g, angelicae 10g, red and white peony root 10g apiece, charred semen arecae 10g, roasted radix aucklandiae 10g, coptidis rhizoma 10g, amoorcorn tree bark 10g, raw astragali 30g, forsythia suspensa 20g, parching atractylodes macrocephala 10g), control group received sulfasalazine (SASP), (4-6g/d). Both treatment course was 3 months, and attended by 6 months partly, mainly observed index: 1. Therapeutic effect, including clinical general effect, change of TCM syndrome, the change of clinical activity index (CAI), endoscopic index (EI) and relapse rate. 2.serum Tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8), serocym interleukin-13 (IL-13). 3.colon mucous membrane Nuclear factor-κBp65 (NF-κBp65) and Epidermal growth factor receptor (EGFR).In animal experiment , the rats were randomly divided into 4 groups: normal group, model group, treated group and Olsalazine sodium group( the controlled group). The last 3 groups are UC rats induced by 2,4,6-trinitrobenzenesulfonic Acid (TNBS) /ethanol mixture. We took serum and colon tissues from 1/3 of the animals every time after giving medicine for 10 days, 30 days and 10 days after stopping treatment. Mainly observed index are: 1.the effects on living state of the rats, the general behaviors and the weight involved. 2. the local pathological change, both gross and microscopic observations. 3. serum TNF-αand IL-8. 4. mucous membrane NF-κBp65, IL-13, Interleukin-1βmessenger Ribonucleic acid (IL-1βmRNA) and Epidermal growth factor (EGF).ResultsEvaluation of therapeutic effect and resisting relapse effect①Clinical general therapeutic effect of treated group is better than control group;Including the total remission percentage of two group, total effective percentage of two group, the statistic significant is difference, treated group is obviously better than control group.②After treatment, the relapse rate in six months of treated group is obviously lower than that of control group.③Syndrome scores of treated group was dropped apparently, the forward improvement of treated group is better than control group.④CAI and EI of treated group significantly dropped after treatment, the forward improvement of control group was better than control group (P<0.01).⑤There was no obvious ill-effect on treated group, which is obviously lower than control group.Researching on mechanism of resisting relapseClinical index:①Serum TNF-αconcentration of patients in UC active phase were remarkablely higher than normal value.Serum TNF-αconcentration in relapse phase of UC patients were significantly higher than that of not relapse patients.After treatment and after six months of attending, serum TNF-αconcentration of treated group were significantly lower than that of control group.②Serum IL-8 concentration of patients in UC active phase were remarkablely higher than normal value.Serum IL-8 concentration in relapse phase of UC patients had no difference from that of not relapse patients.After treatment, serum IL-8 concentration of treated group were significantly lower than that of control group. But after six months of attending, the value of two sets were similar.③Serocym IL-13 concentration of patients in UC active phase were remarkablely lower than normal value.Serocym IL-13 concentration in relapse phase of UC patients were significantly lower than that of not relapse patients.After treatment and six months of attending, Serocym IL-13 concentration of treated group were significantly higher than that of control group. ④Colon mucous NF-κBp65 concentration of patients in UC active phase were remarkablely higher than normal value.Colon mucous NF-κBp65 concentration in relapse phase of UC patients had no difference from that of not relapse patients.After treatment and six months of attending, the value of two sets were similar.⑤Colon mucous EGFR concentration of patients in UC active phase were remarkablely higher than normal value.Colon mucous EGFR concentration in relapse phase of UC patients were significantly lower than that of not relapse patients. After treatment and after six months of attending, colon mucous EGFR concentration of treated group were significantly higher than that of control group.Animal experiment index:①On the aspect of improving the living state, treated group could have obvious effect since the acute period. And improving independence activity, glossiness of coat emerged earlier than control group. Its effect could last to the chronic period and injury recovery period. As the observation of the local colon mucosa, both treated and control group had the effects of inhibiting the injury and and improving the plerosis of mucosa tissues. In acute period, effect of the former inferiored to the latter. But treated group’s effect of improving gt hyperblastosis and forming granuloma surpassed that of control group.②Serum TNF-αconcentration in both treated and control group cut down at the time of treating 10 days. Their effects were similar. Effect of treated group at the time of 30 days and 10 days after stopping treatment was significantly better than control group. Among three periods, value of Serum TNF-αconcentration in treated group was similar to normal group.③Serum IL-8 concentration in both treated group and control group cut down in three periods. Their effects were similar.④Colon mucous IL-1βmRNA concentration in both treated and control group cut down at the time of treating 10 days and 30 days. Their effects were similar. But colon mucous IL-1βmRNA concentration in treated group was significantly lower than that in control group.⑤Colon mucous IL-13 concentration in treated group was significantly higher than that in control group. But effects of cutting down colon mucous IL-13 concentration in both groups at the time of 30 days and 10 days after stopping treatment were similar.⑥Colon mucous NF-κBp65 concentration cut down in both groups at three periods. And effects in both groups were similar.⑦Colon mucous EGF concentration in treated group is significantly higher than that in control group at the time of 10 days. Effect of raising colon mucous EGF concentration in treated group inferiored to that in group at the time of 30 days. Meanwhile, at the time of 10 days after stopping treatment, colon mucous EGF concentration in treated group is significantly higher than that in control group. ConclusionWe have got satisfied therapeutic effect in treating UC by using the methods of profiting Qi, promoting blood flow and detoxifying Du guided by determination of treatment based on differentiation of syndromes. And the therapeutic effect was obviously better than SASP. Especially in the TCM syndrome, CAI, EI, and resisting relapse, showed its superiority. Compared with western medicine, it had no obvious ill-effect. The following is the contra-relapse mechanism of Chinese medicine: 1. Restraining the multi expression of TNF-αand IL-1β, preventing the aggregation of inflamed cell; 2. Raising the expression of IL-13, down regulating the condition of local immunity; 3. Raising the expression of Colon mucous EGF and EGFR since nonage so as to enhance mucosa epithelial cell proliferation, lessen apoptosis, promoting the repair of injuried mucous membrane in later stage.