| Purpose and SignificanceUlcerative colitis (uleerativeeolitis, UC) is a kind of unknown etiology, mainly involving the rectum and sigmoid colon mucosa and submucosa of the superficial, nonspecific inflammatory disease of digestive tract disease, can be extended to the descending colon, the transverse colon, minority can affects the colon, is difficult to cure, often recurrent, is considered to be precancerous lesions of the colon cancer, World Health Organization has been listed it as one of the modern difficult to treat. Modern medicine to UC is lack of a specific treatment, patients often bearing complications, surgery, hormone resistant or dependent abnormal pain, causing severe economic and family burden. Ulcerative colitis is quite common in Western countries, According to the ulcerative colitis-related documents and statistics the number of hospital cases show that its incidence is increasing year by year. Due to the complexity of the pathogenesis of UC, the cause is not yet very clear, due to the lack of effective treatment and specific clinical drug, for some patients accompanied by lifelong with abnormal pain, have serious impact on people’s quality of life. At present, Drugs for UC are often salicylic acid, adrenal corticosteroids, immunosuppressants, etc. Most of them are easy to relapse after treatment, long-term medication side effects, for some stubborn cases, the effect is not ideal shortcomings.In recent years, Chinese medicine in the treatment of UC achieved more satisfactory results, and has little side effects, low recurrence rate and long-term efficacy advantage with better research and development value, favored by the Department of Gastroenterology experts, it is the tracked hotspots in recent years that the Mechanism research on Traditional Chinese Medicine to UC. At present, mechanism on Traditional Chinese Medicine to treatment UC, physicians more emphasis to start from the "Shire" pathogenesis and treatment of diarrhea classic recipe of the "Qinghuashire", such as "Pulsatilla soup","Peony soup","Shenlingbaishu powder" made a lot of achievements. But, according to clinical diagnosis, stagnation and spleen deficiency is important pathogenesis of UC,"Shuganjianpi" is an important method for the treatment of UC, especially the mental factor "liver depression" is probably UC incidence initiating factor, or hard to be cured reasons. The therapeutic principle is the core aspects of connected to the pathogenesis and recipe efficacy, clarify its efficacy mechanism and target of the treatment of UC’s efficacy, from perspective of stagnation and spleen deficiency to study curative effect mechanism of "Shuganjianpi" treatment of UC, can not only expand the idea of Chinese medicine treatment of UC, revealing the scientific connotation of TCM treatments, also provide theoretical support for the development of prevention and treatment of UC proprietary Chinese medicines, all in all, this study has good application prospects and scientific significance and practical significance. Tong Xie Yao Fang from the "Danxi Experiences", composed of four herbs of fried Baizhu, fried Baishao, Fangfeng and Chenpi, its function is Shuganjianpi, it is the classic recipe for diarrhea raised by liver depression and spleen. Reviewed and studied nearly10years ancient and modern literature, it is found that the clinical use Tongxieyaofang or it’s extend recipe for treatment of UC achieved good effect, with good clinical basis, but it is rarely reported of treatment UC mechanism from the experimental perspective. Liver depression and spleen deficiency syndrome is important UC pattern of syndrome, stagnation and spleen deficiency is an important pathogenesis of UC,"Shuganjianpi" is the important treatment of UC, combined with domestic and international fresh research on "Shuganjianpi "treatment mechanism of UC, this study as guide of the "Shuganjianpi" treatment, choice its representative recipe of Tongxieyaofang, aim at basic pathogenesis of UC stagnation and spleen deficiency, focusing on the use of the experimental techniques of molecular biology, from geneand the level of protein expression reveal the TongxieYaofang treatment of the molecular mechanisms of UC, provided experiment basis for the clinical extensive application.Research MethodsThis thesis is divided into two parts, theoretical and experimental studies. The theoretical part finishing medical UC understanding of the basis of the ancient and modern literature, combined with the progress of modern medicine on UC’s research, focuses on TCM etiology and pathogenesis of UC, immunology for UC, UC syndrome type, conquer the logistic regression, the main idea of the treatment of the UC status quo and the thesis Shuganjianpi treatment. First, study part apply the TNBS/ethanol enema rehabilitation UC rat model of experimental, in the modeling of different time periods by RT-PCR, Western blot and ELISA, immunohistochemistry technology dynamic observation of rat colon tissue of PPAR-γ, NF-κB p65, ICAM-1and serum IL-1β, TNF-α, dynamic expression, and to explore its role in the pathogenesis of UC. Followed by research to establish the rat liver depression and spleen UC model TNBS/ethanol+binding method+diet disloyal composite method and treatment to give TongxueYaofang intervention, observation of UC colon tissue of PPARγ and NF-κB p65, ICAM-1content and the level of serum IL-1β, TNF-α, on the one hand, looking for a new role in the treatment of UC target, other hand, from the genetic level to further explore the mechanism of action of the Shuganjianpi treatment of UC, to provide a theoretical basis for its clinical application and development of new compound Chinese medicine.Conclusions and Significancea. TNBS/ethanol enema can be successfully established rat model of UC, observation from naked eye and microscopic, all showed inflammation and ulcers, and colon injury are dynamic modeling time trend, which is most severe lesions3d and7d,14d and21d days, some repair of the inflammation and ulceration would be appear.b. In the acute phase of the UC model, PPARγ expression in colonic tissue was significantly reduced, the chronic phase PPARγ expression slightly elevated, but still lower than the blank group. UC model of the acute phase of NF-κB p65and ICAM-1expression was significantly increased in the chronic phase of NF-κB p65, ICAM-1expression slightly reduced, but still significantly higher than the blank group.c. Proinflammatory cytokines TNF-α, IL-1β and anti-inflammatory cytokines IL-4balance involved in the occurrence of UC development.d. PPAR-γ expression and colon tissue injury, IL-1β, TNF-α, NF-κB of p65, ICAM-1expression was negative correlation of different.e. The occurrence and development of UC inhibited the expression of PPARγ is closely related to raised expression of PPAR-γ is expected to become the new targeted treatment of UC.f. Liver stagnation and spleen deficiency is an important pathogenesis of ulcerative colitis; stagnation and spleen deficiency is important pathogenesis of UC,"Shuganjianpi" is an important method for the treatment of UCg. Tong Xie Yao Fang has protection and repair function for the model of stagnation and spleen deficiency UC colon tissue, the molecular mechanism is up regulated PPAR-y mRNA and protein expression, inhibition of the colonic tissues ICAM-1, NF-κB p65mRNA and protein expression, suppression of serum IL-1β and TNF-α expression, so as to reduce the inflammatory reaction, and play a role in the treatment of UC. The TongXieYaofang may have PPAR agonist’s utility. |
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