Study On The Effect Of KJT On NFκB In Intestinal Mucosa Of Rats With Ulcerative Colitis

Objective: The initiating event and pathogenesis of ulcerative colitis (UC) currently remains extremely elusive, but our understanding of cellular and molecular mechanisms associated with UC has increased dramatically. Increasing evidence points to cytokines as contributing to the pathogeni- c cascade that initiates and perpetuates UC. Inhibition of proinflammatory cytokines has been found to reduce inflammatory in various animal models of gut inflammatory based on these observations, a rationale for cytokine-targeted therapy for UC has been established and clinical studies have been initiated by using anti-tumor necrosis factor(TNF)- α antibody or interlenkin(IL)-1.Recent investigations have focused on transcription factors that regulate production and activation of cytokines including the nuclear factor-κB, the p38 mitogen-activated protein kinase, the peroxisome proliferator-activated receptor, and the janus kinase/signal transducers and activator of transcription pathways. Although their exact role in UC is still unknown, further studies may lead to identification of additional possible targets for therapeutic intervention that could improve management of the disease.Rogler described for the frist time the actioation of NF-kappaB during human mucosal inflammation in situ by immunohistochemical analysis and electrophoretic mobility shift assay. In addition to macrophages, epithelial cells contained activated NF-kappaB. This study shows transcription factors of the nuclear factor kappaB family play an important role in the regulation of genes involed in inflammation of UC. Murano has demonstrated on mouse dextran sulphate sodium(DSS)-induced colitis that intracolo- nic administration of NF-kappaB antisense oligonucleotide may be effective in UC . After investigated the activation and expression of NF-κB and effects of anti-inflammatory treatment of sulphasalaine(SASP) and glucocorticoids in the intestinal mucosa of patients with UC, Gan concluded (1) The increased activation of NF-κB and increased expression of NF-κB might be involved in the pathogenesis of UC; (2) Glucocorticoids and SASP strongly inhibited NF-κB activation and expression. The inhibition of NF-κB activation might be a central part of the anti-inflammatory action of glucocorticoids and SASP, which might represent an import- ant pharmacological mechanism in treatment of patients with UC. NF-κB will be an important target for cytokine-based therapy of UC.Recently, there is not report about the role of NF-κB in the intestinal mucosa of rats with UC in native county. This study was designed to investigated the activation andexpression of NF-κB and effects of anti-inflammatory treatment of traditional Chinese medical complex kuijietang (KJT) in the intestinal mucosa of rats with UC. Methods: 1. Induction of UC rats model: Selecting 50 health adult Wistar rats whose weight were between 270±20g (female and male half respectively), we induced rats model with Cellular immunoreactive UC by compound method (2,4-chlorodinitrobenzene and acetic acid). 2. Animal groups distribution and treatment: 40 UC Wistar rats induced were divided randomly into model group, low dose KJT group, high dose KJT group and SASP group, while there were 10 normal Wistar rats in control group. Rats in low and high dose KJT group had been respectively administrated KJT at an average dose of 10g/kg and 20g/kg body weight each day by stomach perfusion for 2 weeks, and rats in SASP group had been administrated SASP tablets dissolved with distilled water at an average dose of 0.2g/kg body weight each day by stomach perfusion for 2 weeks. Rats in Model group and control group have been administrated equal physiological saline for 2 weeks. The clinical situation of rats had been observed each day.