| Ulcerative colitis is a chronic disease with characteristics of pathological changes of large intestinal mucosa and the inflammation of submucosa. It is hard to cure, and liable to relapse. Part of the patients may suffer from the disease all their life long, which brings great pain to the patients. So the disease is considered as the precancerous lesion of cancer of colon, which has been taken as one of diseases difficult to cure in modern times by the World Health Organization. Ulcerative colitis is relatively common in western countries. In Asian countries, it is supposed that the disease is rare in the past, but in recent years, the report cases increase with years. In our country, there is no prospective investigation on ulcerative colitis epidemiology. But relevant documents and statistics on ulcerative colitis cases in hospital show that the morbidity increases with years, which has seriously affect quality of life of people.The pathogenesis of ulcerative colitis has not been elaborated till now,but the important role of immunity factors in ulcerative colitis has been universally acknowledged by a great number of scholars,namely abnormal immunity refection or the destroy to normal immunity adjustment is an important tache for the morbidity of ulcerative colitis. At present, the pathogenesis is supposed as the environmental factors acting on the genetic susceptible individuals, and then activating lymphocyte and macrophage to release a series of inflammation mediators and cytokines;all these inflammation mediators and cytokines can further mediate and adjust immunological reaction,thus leading to cell immune reaction and humoral immune reaction and expansion and continuance level by level, further causing damage to intestines and a series of clinical manifestation. PPAR-γas a nuclear factor which activated by ligand,has many biological effects.It interacts with special PPRE on upper of some genes to adjust gene expression. According to the research, PPAR-γplays a very important role in adjusting fat metabolism,insulin sensitization, inflammation reaction, atherosclerosis and cell proliferation and differentiation, which has close correlation with the happening and development of ulcerative colitis. PPAR-γcan inhibit the transcription and signal transduction of NF-κB and adjust the expression of inflammatory factors,which might inhibit local inflammatory reaction.It plays a important role in the happening and development of ulcerative colitis.There are less really therapeutical remedies for ulcerative colitis yet at present. Chinese traditional medicine,with relatively less side effects and recurrence rate, high prostecdtive efficacy,can regulate physiological reactions into balance by more targets. The most treatment of ulcerative colitis with Chinese traditional medicine are confined to observations of therapeutic effect,but less investigations on the mechanism of action in recent years. While,reports about studying effects of Chinese traditional medicine on expression of PPAR-γare rare. Changkang Keli (CKKL) is a experienced prescription designed by tutor and gained some fine clinical therapeutic effects. But its exact mechanism of action is still not clear now.In our study, we reproduced the ulcerative colitis models with TNBS plus alcohol. During the different stages of the models (3d,7d,14d,21d), we observed the dynamic expression of PPAR-γand NF-κB p65 in colonic tissue of rats through molecular biology and immunohistochemistry technique.At the same time,we also detected the level of IL-1βand TNF-αin serum, the content of ICAM-1 in colonic tissue. Then we analyzed the dependablity between the expression of PPAR-γand other indexes,in order to identify the possible roles of PPAR-γin ulcerative colitis. Moreover, we treated ulcerative colitis animals with low,middle and high dosage CKKL and SASP for 21d. Then we observed the expression of PPAR-γand NF-κB p65 in colonic tissue,the level of IL-1βand TNF-αin serum,the content of ICAM-1 in colonic tissue,in order to observe the effects of CKKL on the expression of PPAR-γand its therapeutic effect, approach its mechanism of action initially.The following is the study outcomes:1. Rat models of ulcerative colitis were replicated successfully.There occured obvious inflammation and ulcer in naked eyes and microscope.There were acute manifestations in 3d and 7d groups, and the 14d and 21d groups transform to chronic gradually.2. In acute period, PPAR-γin colon tissues expression reduced gradually.With the transformation to chronicity of ulcerative colitis,PPAR-γexpression increased gradually,but it was still lower than alocohol control group.3. In acute period, NF-κB p65 in colon tissues expression increased gradually. With the transformation to chronicity of ulcerative colitis, NF-κB p65 expression reduced gradually,but it was still higher than alocohol control group.4. In acute period, IL-1βand TNF-αlevel in serum and the content of ICAM-1 in colon tissues increased obviously. With the transformation to chronicity of ulcerative colitis,all indexes reduced gradually,but they were still higher than alocohol control group. Among them,peak of IL-1βappeared in 7d group, peak of TNF-αand ICAM-1 appeared in 14d group.5. Analysis of dependability indicates that the gene expression of PPAR-γ in colon tissues was correlated with the degree of colon injury,expression of NF-κB p65, IL-1β, TNF-αand ICAM-1 negatively.6. CKKL could make PPAR-γexpression in colon tissues increase up,and reduce the NF-κB p65, IL-1β, TNF-αand ICAM-1 expressions.CKKL might protect and repair the damaged colon tissues,which was superior to SASP.The study results suggested that:1. PPAR-γplays an important role in ulcerative colitis. PPAR-γexpression is restricted, which could promote the happening and development of ulcerative colitis through increasing up NF-κB p65, further increasing up IL-1β, TNF-αand ICAM-1 expressions.Increasing up PPAR-γexpression is hopeful to become a new target to cure ulcerative colitis.2. CKKL has good therapeutic effect on ulcerative colitis, and PPAR-γmay be a main target of its effects. Increasing up PPAR-γexpression can inhibit NF-κB p65 expression, further reduce IL-1β, TNF-αand ICAM-1 expresions. It may be one of important mechanism of action of CKKL.Innovation of the study:1. Adopting RT-PCR technology to observe dynamic expression of PPAR-γin the different stages of rat ulcerative colitis induced by TNBS. Analysis of dependability indicates that the gene expression of PPAR-γmRNA in colon tissues was correlated with the degree of colon injury,expression of NF-κB p65,IL-1β,TNF-αand ICAM-1 negatively.2. Approaching the mechanism of CKKL to ulcerative colitis from the level of gene and protein.CKKL can increase up PPAR-γexpression,inhibit NF-κB p65 expression,further reduce IL-1β,TNF-αand ICAM-1 expresions,then play its anti-inflammatory effect and gain fine therapeutic effect.
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