| ObjectiveThe etiology and pathogenesis of ulcerative colitis (UC) is not very clear. In recent years, with in-depth study of ulcerative colitis, the incidence and treatment of ulcerative colitis have a new understanding that regardless of the primary lesion of the intestinal tract, or consequential damages, would result in the colon closely related to the mucous membrane structure and function of injury in the pathogenesis of ulcerative colitis. Mucosa is not only an important place of nutrient digestion and absorption but also pathogenic microorganisms and toxins to invade the main portal.Under physiological conditions, the body through the mucosal barrier to effectively prevent the invasion of pathogenic microorganisms and toxins in order to ensure that the body in a healthy state. Microorganisms and toxins can break through the intestinal mucosal barrier into the portal vein and the lymphatic system. They also can cause bacterial translocationand the development of ulcerative colitis.To explicit inflammatory cells regulating factor of NF-κB, β-defensin-2, TFF3,EGF and TGF-beta in intestinal self-protection and damage repair mechanisms, the subject of high-fat high-sugar diet plus TNBS enema copy ulcerative colitis rat model and tracking them back in the colonic mucosa damage, the study focused on the regulation ofinflammatory cell factor NF-κB transcription factor. In the intestinal repairing, the study focused on the β-defensin-2, TFF3and EGF and TGF-beta in the Ulcerative Colitis change and relatedregulation mechanism in the development and mucosal repair process. Through observation the Modified Pulsatilla Decoction on the NF-κB activation and β-defensin-2, TFF3and TGFβ1,EGF expression, and then explore the intestinal injury and repair mechanism of the Added Pulsatilla Decoction on ulcerative colitis, and to provide theoretical foundation on Added Pulsatilla Decoction used in ulcerative colitis clinical.Methods40of SPF health SD rats were randomly divided into normal control group, model group,the sulfasalazine group, Added Pulsatilla Decoction group.(N=10). Trinitrobenzene sulfonic acid (TNBS) local enema plus high fat and sugar established the UC rat model. After the success of produced Animal model,the treatment group given modified the Pulsatilla soup gavage, the comparison group given sulfasalazine (SASP) orally once a day, model group and normal control group given the same volume of of normal saline once a15d. After end of treatment, rats were fixed on the rat of dissecting table, the intraperitoneal injection of20%urethane anesthesia, dissected the entire colon tissue, first carefully observed by the naked eye the colonic mucosa of rats in each group congestion, edema, pseudomembranous, ulcers and erosions.The number and size of the pathological changes, and then take a small amount of colonic mucosa tissue embedded in paraffin, HE staining and observed by light microscopy, the pathological changes of rat colon tissue. The remaining colonic mucosa specimens using Western blot (Western blot analysis) assay of NF-κB protein expression levels, Real-time PCR method for determination of (3-defensins-2TFF3gene expression changes in the immunohistochemical method observation of TGFβ1and EGF changes in protein expression.Results1Compared with model group, the general situation in Added Pulsatilla Decoction group was significantly improved, in rat blood and pus and mucus disappeared, stool forming, flexible activities, improved appetite, body weight of rats was significantly higher. Added Pulsatilla Decoction group can make the intestine mucosal injury and histological score lower, compared with model group, the difference was significant (P<0.01). Intestine mucosal congestion, edema, pseudomembranous, ulcers, and erosion number and size were reduced, intestinal damage were repaired, inflammatory cell infiltration were reduced, ulcer mucosa can be seen near continuous mucus layer covering the submucosa visible collagen fibers.2Compared with normal group, the model group rats of NF-KB of p65expression significantly with increased,(P<0.01); given to the treatment of Added Pulsatilla Decoction, NF-κB of p65expression was significantly decreased, compared with model group, the differences was significant (P <0.01); treatment group and comparison group showed no significant differences (P>0.05).3Compared with normal group, model group rats colonic mucosa beta-defensin-2expression was significantly higher, the difference was significant (P<0.01); give Added Pulsatilla Decoction treatment, the colonic mucosa beta-defensin-2gene expression was significantly decreased. Compared with model group, the difference was significant (P<0.01), treatment group and comparison group showed no significant difference (P>0.05). 4Compared with the normal group, the model group rat colonic mucosa ITF decreased slightly, but no significant differences (P>0.05); given Added Pulsatilla Decoction treatment, the colonic mucosa TFF3gene expression increased significantly compared with the model group, the difference was significant (P<0.01); treatment group and comparison group showed no significant difference (P>0.05).5Compared with the normal group, model group TGFβ1of expression was significantly increased, the differences was significant (P<0.01), to give Added Pulsatilla Decoction treatment of TGFβ1is relatively express the amount for the significantly decreased, compared with model group,the differences was significant (P<0.01), treatment group and western medicine in the control group showed no significant difference (P>0.05). Compared with the normal group, model group, EGF expression was significantly lower than the normal group, the difference was significant (P<0.01); give Added Pulsatilla Decoction treatment of EGF protein relative expression was significantly increased compared with model group, the difference was significant (P<0.01), treatment group and comparison group showed no significant difference (P>0.05).Conclusion1The Added Pulsatilla Decoction can inhibit the inflammatory cell infiltration of the UC, reduced the inflammation, as well as promote the repair of the colonic mucosa damage and restore the secretory function of the colonic mucosa. The model of UC were copied successfully. The Added Pulsatilla Decoction can reduce colonic inflammation, promote colonic mucosa repair, and thus play a role in the treatment of UC.2Have a certain relationship between the NF-κB p65expression and UC disease severity and activity, suggesting that the organization of the UC colonic mucosa of NF-KBexpression level may reflect the extent of damage of the colon tissue, the judgment of the condition assessment and treatment effects may potentially guidance. The Added Pulsatilla Decoction can inhibit the excessive activation of NF-KB on UC rat model, which may be one of the mechanisms of the Added Pulsatilla Decoction group on the treatment of UC rats.3The Added Pulsatilla Decoction of therapeutic effect may be that the content by down-regulating β-defensin-2gene expression, and thus reduce the inflammation of thecolonic mucosa, destruction of intestinal pathogenic microorganisms, play a role inmucosal repair. beta-defensin-2may be the role of key target by Added Pulsatilla Decoction treatment of UC4The Added Pulsatilla Decoction can increase the TFF3secretion in the colonic epithelial cells and to promote tissue repair of the damaged colonic mucosa.5The Added Pulsatilla Decoction can downward TGF(31protein expression of the UC rat,and inhibit the inflammation development. The Added Pulsatilla Decoction can increase the EGF protein expression of UC rat, can contribute to the damaged mucous membrane surrounding the integrity of the epithelial cells to injury the migration of the mucosal surface coverage, accelerate the repair of damaged mucosa. |
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