Effect Of The NF-κB(p65) Inhibitor On Endotoxin-Induced Uveitis

Objective:Immuning SD rats with the lipopolysaccharide(LPS),and establishing a uveitis model and this afford a worthy tool for experimental study of immunogenic and therapy of uveitis.Endotoxin-induced uveitis (EIU)is a model for acute panvueitis seen in human. We report a study of the effect of systemic administration of PDTC on the clinical presen- tation ,histopathologic change and the level of Toll- like receptor-4(TLR-4) on iris in the SD rats.Methods: The establishment of endotoxin-induced uveitis disease model.Female SD rats(180～200g) were selected between 6～8 weeks age. Twelve SD rats were randomly divided into the healthy control group (6 rats,group 1A) and the experimental group(6 rats, group 1B). Lipopoly- saccharides were dissolved in the sterile,pyrogen-free 0.9% saline at a con- centration of 2 mg/ml,and 50μl was injected into each hind footpad of Sdrats in the experimental group (200ug total does per rat).The rats in the healthy group were injected 0.9% saline 200μl per rat in the same way. Twenty-four SD rats were randomly divided into three groups,including the EIU group(6 rats, group 2A),PDTC group(6 rats, group 2B)and Dexa- meth- son group(6 rats, group 2C).200μg of Lipopolysaccharide were inject- ted into footpads of each SD rats in all groups. The rats in group 2A were subconjunctival injected with 0.9%salin at 1ml/kg twicely at the time of 0h and 6h after lipopolysaccharide injection.Both rats in group 2B with PDTC at 20μg/kg and group 2C with Dexa at 100μg per rat were injected in the same way.All samples were examined with light microscope in 6h,12h,18h, 24h after LPS injection.The numbers of leukocyt and concentration of pro- tein in aqueous humor were measured and TLR-4 in iris constitution were observed by immune-histochemistry after rats had been killed in 24h.Results:The data was denoted by x±s, and analyzed the data by SPSS 11.0 software.The EIU disease model was established successfully in SD rats in this study.The disease incidence was 100%.The clinical and histolo- gical features were stable.Obvious uveitic inflammatory signs such as flare,cells and protein exudates in anterior chamber,occlusion of pupil and vitreous opacity were obserbed.The quantity of leukocyt and protein obv- iously decreased in group 2B and 2C,p<0.05.And so was TLR-4 on iris in the same group.But there was not significant differences between 2B and 2C,p>0.05.Conclusions:1.Uveitis with marked clinical signs is successfully indu- ced in the SD rats with injection of LPS.2. TLR-4 expression increased in the control group. TLR-4 probably participates in the formation and dev- eloppment of acute anterior uveitis.3.PDTC could relieve inflammatory reaction and TLR-4 expression decreased in the PDTC group. 4.Dexa- methason could obviously suppress the symptom of EIU relieving infla- mmatory reaction and could decrease the expression of TLR-4 on iris.