Influence Of Rosiglitazone On The Expression Of PPAR γ, NF-κB And TNF-α In Rats Model Of Ulcerative Colitis

Objective: Ulcerative colitis (UC) is one of the inflammatory bowel diseases which is characterized by invading mucosa and submucosa predominantly. The current opinion about the pathogenesis of UC is that the imbalance of pro-and anti-inflammatory cytokines plays a critical role and peroxisome proliferators-activated receptor gamma (PPARγ) participates the regulations of intestinal inflammation. This study was aimed to observe the disease activity and colonic mucosa damage, to detect the expression of PPARγ,NF-κB,TNF-αand to explore the possible therapeutic mechanism and effects of rosiglitazone in rats model of ulcerative colitis so that rosiglitazone could be possibly used in the clinical treatment of UC in the future.Methods: 108 male SD rats were randomly divided into three groups of 36 rats each: normal group, rosiglitazone-treatment group, model group. The rat model of ulcerative colitis was established with TNB/ethanol complex method except the normal group which was clystered with normal saline instead. Rosiglitazone(8mg/kg) was administered intragastrically to the rosiglitazone-treatment group once a day and normal saline was administered to normal and model group as controls. Observe the general states of rats model of ulcerative colitis and evaluate the disease activity index (DAI) everyday. Six rats from each group were sacrificed respectively on the day of 3, 7, 14, 21, 35, 56 after clyster and then segments of colon were obtained. Light microscope was used to evaluate the colonic mucosa damage index (CMDI), Hematoxylin-Eosin(HE) staining was applied for pathological study, RT-PCR and IHC methods were utilized to detect the expression of PPARγ, NF-κB, TNF-αon the levels of mRNA and protein.Results:1. The scores of DAI, CDMI were significantly increased in the model group as compared to those in the normal group at the same time period (p<0.05). The scores of DAI, CDMI on the day of 14, 21, 35, 56 were significantly decreased in the rosiglitazone group as compared to those in the model group (p<0.05)2. The expression of PPARγwas significantly decreased in the model group as compared to those in the normal group on the levels of mRNA and protein at the same time period (p<0.05).The expression of PPARγon the day of 7,14, 21, 35, 56 was significantly increased in the rosiglitazone group as compared to those in the model group on the levels of mRNA and protein at the same time period (p<0.05).3. The expressions of NF-κB, TNF-αwere significantly increased in the model group as compared to those in the normal group on the levels of mRNA and protein at the same time period (p<0.05). The expressions of NF-κB, TNF-αon the day of 7, 14, 21, 35, 56 were significantly decreased in the rosiglitazone group as compared to those in the model group on the levels of mRNA and protein at the same time period (p<0.05).4. There were significant correlations between the expression of NF-κB and PPARγ,NF-κB and TNF-α, their correlating factors were -0.881, 0.943 respectivly(p<0.05).Conclusions:1. PPARγhas the protective effect in the rats model of ulcerative colitis, NF-κB has the indirect inflammatory effect in the rats model of ulcerative colitis.2. Inhibition of PPARγmay be correlated with NF-κB activation and causes excessive expression of inflammatory cytokine, leading to colonic tissue damage and aggravation of the disease.3. Rosiglitazone promotes the expression of PPARγto inhibit the activation of NF-κB and to alleviate inflammatory response in colonic mucosa. Rosiglitazone eases inflammatory syndrome in rats model of ulcerative colitis,especially in the chronic phase of ulcerative colitis.