| Background and aim: Rheumatoid arthritis(RA) is a chronic,systemic,autoimmue disease with anunknown etiology.Both genetic and environmental factors contribute to diseasesusceptibility.It is characterized by joint pain and swelling,joint destruction and pannusformation.The severity of the joint disease may fluctuate over time, but the mostcommon outcome of established disease is progressive development of various degreesof joint destruction, deformity, and disability. Radiological damage occurs early indisease; approximately 30% of patients will develop bone erosions within 1 year ofdisease onset and this percentage increases to 70% by 3 years. Untill now no any drughas been found to cure RA,Howerver, In recent years, several studies have shown that agreater impact on slowing disease progression can be achieved if patients with RA aretreated with DMARDs treatment within 3 months of diagnosis. Response of earlytreatment directly influences on the prognosis of RA. MTX is an antagonist of folate with a potent immunosuppression andanti-inflammation. It is commonly used as the first-line DMARD , has a welldocumented clinical efficacy and slows radiological deterioration in RA. Sinomenine is extracted from the Chinese medical plant Sinomenium acutum,which has been utilized by Chinese doctors for more than 1000 years to treat variousrheumatic diseases.Previous studies have demonstrated that sinomenine amelioratesexperimental arthritis in rat such as CIA(collagen induced arthritis) ,AIA(antigeninduced arthritis) and AA(adjuvant arthritis).The effection of Sinomenine on theprevention of PIA(pristane induced arthritis) in rats remains undefined.It is unclear ifsinomenine ameliorates the progression of RA. Pristane induced arthritis in rats is a chronic, relapsing and progressive arthritis thatclosely mimics RA.It is believed to be a CD4+T cell mediated autoimmmue disease. PIA in rats was chosen as a RA model to investigate Sinomenine and MTX on theprevention of RA. Methods: Forty Female Lewis rats were averagely divided into 5 different groups accordingto the treatment project at random:normal group,model group,MTX-treatedgroup,Sinomenine-treated group and MTX+ Sinomenine- treated group. All rats exceptnormal group were intradermally injected with 0.2 ml pristane at the base of the tail,andnormal control rats were injected with 0.2ml 0.9%NaCl.Rats in normal group and modelgroup were given 0.9%NaCl (10ml/kg/d)orally, rats of other groups were orallyadministered sinomenine (120mg/kg/d) and/or MTX(3.8mg/kg/w),thereafter through 8weeks.Arthritis development was monitored by a macroscorpic scoring system for thefour limbs ranging from 0 to 4.Bone and cartilage destruction in rats was assessed byradiographic and histological methods.Serum was collected on week 0,1,3,5,8 afterimmunization and was stored at -80℃. On the week 8 ,the rats were killed under etheranesthesia and the right paw were fixed in 10%formalin phosphate.The inguinal lymphnodes and synovium of left ankle were isolated from the individual rats and stored at-80℃.The concentration of serum IL-6 and IL-10 were determined byradioimmunization essay,serum TIMP was by ELISA.Total RNA was extracted withTrizol,and then IL-4,IL-10 and IFN-γ mRNA was half-quantified using RT-PCR.PCRproducts were stained with ethidium bromide and quantified with fluorescence imageanalysis. Results: 1.In PIA model group,the incidence of arthritis was 62.5%,peripheral joints weremainly involved ,the arthritis developed suddenly and dramatically 2 weeks afterpristane injection and gradually subsided 3 weeks later.However, chronic relapse startedat 6-8 weeks after pristane injection.As showed by histopathology and roentgenography,typical arthritis pathology such as synovial proliferation,erosive articular cartilage andbone was found. 2.Incidence of PIA in Sinomenine-treated group was 75%, its arthritis indexshowed no significant differences in comparison with PIA model group; Incidence ofPIA in MTX-treated group was 12.5% and equal to that in sinomenine + MTX-treatedgroup,their art...
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