Intervention effect of proteasome inhibitor MG132 in rats with collagen-induced arthritis / 中国免疫学杂志

ABSTRACT

Objective:To explore the intervention effect of proteasome inhibitor MG132 in rats with collagen-induced arthritis(CIA),which resembles human rheumatoid arthritis(RA).Methods:Forty-eight female SD rats were randomly divided into three groups,including blank control group,CIA model group and MG132-treated group.There were sixteen rats in each group.Rats in CIA model group and MG132-treated model group were injected with type Ⅱ collagen to established CIA rats.21 days after the initial immunization,the rats in the MG132-treated model group were injected subcutaneously with 1 mg/kg MG132 once daily for 2 weeks.42 days after the initial immunization,the change of paw-swelling and the arthritis scores were determined.The synovial pathology examination was performed with HE staining.The 20S proteasome activity in synovial tissue was measured by fluorescence substrate assay.The expression of NF-κB/p65,IκBα in synovial tissue were analyzed by Western blot.Results:Proteasome inhibitor MG132 significantly attenuated the severity of arthritis and histopathological changes in CIA rats.Compared with the blank control group,the 20S proteasome activity was increased significantly in the CIA model group(P<0.05),and decreased after injection of MG132.Compared with CIA rats,the expression of NF-κB/p65 significantly decreased in rats treated with MG132(P<0.01).Compared with the blank control group,the expression of IκBα protein decreased in CIA model group.After injected with MG132,the protein was significantly increased(P<0.01).Conclusion:The proteasome inhibitor MG132 may attenuates the severity of arthritis and histopathological changes in CIA rats.These effects may be mediated through the inhibition of NF-κB activity.