Study On The Effect Of KJT On MMP-9 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 infla- mmatory in various animal models of gut inflammatory based on these observations.Matrix metalloproteinases (MMPs) belong to the major enzyme group capable of degrading extracellular matrix (ECM) and basement membrane components. They play significant roles in fetal development, tissue remodeling, tumour invasion, wound healing, inflammatory and angioge- nesis. The expression of most MMPs is regulated at the transcriptional level by a variety of cytokines and growth factors. MMPs are secreted as latent precursors or zymogens, most of which are proteolytically activated in the extracellul- ar space or on the cell membrane. Their activity is controlled by the above-mentioned activation mechanisms and by specific tissue inhibitors of metalloproteinases (TIMPs) andnon-specific inhibitors, e.g. α2-macroglobulin. Expression of MMPs protein is detectable in low level in normal tissue, while in response to proinflammatory cytokines such as interleukin(IL)-1 and tumor necrosis (TNF)-α ,their express- ion are increased. The balance between MMP and TIMP is changed, which exacerbates degradation of ECM. Subsegue- ntly, structure of tissue is destructed and/or tissue is remodeled, which cause function disabled. UC are histologically characterized by continuous or discontinuous mucosal in inflammatory with subsequent ulceration and fibrosis involving different depths of intestinal wall.recent evidence shows that proteolysis of the mucosa may occur in UC. Increased MMP-3 and MMP-9 expression shown by immunohistochemixtry has also been found in regions of mucosal damage in UC. MMP-9 facilitates the leucocyte extravasation and permeation of serum proteins into surrounding tissue.Recently, there is not report about the role of MMP in the intestinal mucosa of rats or human with UC in native county. This study was designed to investigated the express- ion of MMP-9 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 ratsmodel 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. Then anesthesia agent Chloral Hydrate(350mg/Kg body weight) was injected in the rats abdominal cavity. Took out 2-10cm colon fr...