Role Of Probucol In Resolution Of Monosodium Urate Monohydrate Crystal Induced Acute Gouty Arthritis Of Rat

Objective:To study the feasibility and mechanism of Probucol in resolution of monosodium urate monohydrate(MSU) crystal-induced arthritis.Methods:1.60 Wistar male rats were fed adaptive one week,and then were randomly divided into 6 groups:the control group,model group,High-Medium-Low dose probucol groups and Colchicine group.A rat model of acute gouty arthritis was induced with the injection of MSU into rat ankle joint cavity.Control group,intra-articular injection of control solution,others groups were injected MSU.At the same time,given the drug treatment group administered 3 days.The effects of Probucol on arthritis were investigated through observing clinical features at 2,4,6,10,24,48,72 hours,and also observing the synovial fluid white blood cell count,interleukin-1β(IL-1β),MDA and SOD at 72 hours.It was observed the synovial tissue inflammation by HE staining. 2.IL-1βconcentration of culture medium was observed after the 18h intervention with Probucol in THP-1 monocytes while stimulated by MSU.Results:1.The degree of joint swelling decreased gradually from Probucol low-dose group to high-dose group and there was signifanct difference between mid-dose and hign-dose Probucol groups and model group at 72h(P＜0.05).The synovial fluid white blood cell count and IL-1βdeclined in varying degrees in Probucol groups when comparing with the model group.Synovial fluid white blood cell count of Probucol mid-dose and high-dose group decreased significantly,comparing with the model group (P＜0.01,P＜0.001),MDA decreased significantly(P＜0.001)and SOD increased(P＜0.01). IL-1βof Probucol high-dose group decreased significantly comparing with the model group the model group(P＜0.05).The model rats had congestive hyperplasia synovial tissue,and obiously an increase in leukocyte infiltration.High-dose probucol group significantly reduce inflammation 2.Probucol groups have no inhibition on IL-Iβsecretion of the THP-1 human monocyte cells comparing with the model group experimental control group(P＞0.05).Conclusion:The mid-dose and hign-dose Probucol can effectively control acute gouty arthritis attack and the effect is dependent on dose,and the effect was not produced by inhibiting IL-1βsecretion of THP-1 monocytes after the uptaking the MSU.