Tripterygium Wilfordii In Rheumatoid Arthritis, The Mechanism Of Action

OBJECTIVE: Rheumatoid arthritis (RA), a common and severe disease, is a chronicinflammatory disease of unknown cause, which is characterized by synovialhyperplasia, inflammation, and joint destruction. Its prevalence in adults inChina is about 0.32-0.35%, which is lower than that in America 1% . And it isone of major diseases causing disability in our nation.The major pathologicalchange of RA is synovitis, with the invasion of cartilage and joint. Among somany factors causing RA, cytokines and MMPs are critical to the occurence anddevelopment of RA.Moreover, more scientists increasingly par attention to thesignal traduction related to RA, since many factors have to work via thesepathways. The Chinese Medicine Tripterygium Wilfordii Hook F (TWHF) is one ofthe most effective medicines for RA, which has been applied in clinics forseveral years. However, the mechanism of its treatment are still unclear.Inour studies we paln to explore such mechanism of TWHF in RA from three aspectsby using the pathological models of AIA rats and FLS of RA patients: the effectsof TWHF on CKs in the serum of AIA rats; the effects of TWHF on the balanceof MMPs and TIMPs in the serum of AIA rats; the influence of TWHF on thephosphorylation of ERK in FLS of RA patients.METHODS: By using the pathological models of AIA and FLS of RA patients, westudy the mechanism of TWHF in RA disease. There are three parts in my thesis.The first and second ones are carried out by using the animal models. The Wistarrats are grouped randomly into three groups: negative control group; AIA group;group with treatment of TWHF.In the first part,the AIA rats was feed by TWHF20mg/kg every day for 21days. During this period, the changes of the generalstatus, swelling, weight of the rats have been recorded on different time. After21 days of treatment, the rats were put to death and the serum was collected.And then in the following experiments, the content of IL-4, IL-10, IFN-γ, NOand IL-1 in the serum of AIA rats has been detected. In the second part, thecontent and activity of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the serum of AIArats were detected respectively. The finally part of my experiments are carriedout in the FLS of RA patients. The effect of TWHF on phosphorylation of ERKinduced by IL-1 has been detected. RESULTS: The result of the first experiment suggests that TWHF has manifesteffect on the swelling of AIA rats. After two days building the AIA models,the original swelling of AIA rats is manifest with comparing normal rats(P<0.01). And after 15 days, the secondary swelling of AIA rats was manifestthan those normal ones(P<0.05). After the treatment of THWF for 21days, boththe original and secondary swelling were improved with comparing with AIAones(P<0.05). Moreover the content of IL-1,NO and IFN-γin serum of AIA ratsare more than those in normals(P<0.01); whereas the content of IL-4 and IL-10are lower than those in normals (P<0.01). And TWHF can deduce the content ofsuch inflammary cytokines (P<0.05), however the IL-4 and IL-10 did not deducemanifest. (P>0.05) On the second one, the content and activity of MMP-2 and MMP-9 in serumof AIA rats are higher than those in normals (P<0.01 and P<0.05); whereas thecontent and activity of TIMP-1 and TIMP-2 were lower than those in normals.After the treatment of TWHF for 21 days, the content and activity of MMP-2 andMMP-9 in serum of AIA rats were deduced (P<0.05), whereas the content andinhibit the activity of TIMP-1 in serum of AIA rats were relatively high withregarding to normals (P<0.05). However TIMP-2 varied little (P>0.05). On the third one, the result showed that the phosphorylation of ERK inducedby IL-1 in FLS of RA patients was inhibited respectively by TWHF 5ng/ml and10ng/ml.CONCLUSION: from the there parts, we can draw such conclusion that TWHF haseffective treatment on both AIA and RA. Futhermore, the targets of TWHF in RAandAIA aremultiple,butnot limitedin specialones. TWHFcandeduce thecontentof IL-1 and NO effectively. Moreover, it is also helpful to adjust the balancebetween of MMPs/TIMPs. Such adj...