Mechanism Reserch Of Bitongling Granule On Protection Of Synovial Membrane In Rheumatoid Arthritis

Background:Rheumatoid arthritis(RA) is one of the systemic autoimmune disease characterized as non-infection inflammation in joint and tissue around joint. The pathological features of RA is the chronic inflammation, cellular infiltration, invasion of gristle and bone and destroy the structure of the joint. RA is still a difficult disease for treatment and no special treatment. The Chinese Herbs was accepted by patients because it can regulate the body function with stable effect and less side effect.Rationale of Research:RA manifested as joint swelling and pain, stiffness and joint malformation clinically, which belongs to "Bi" Syndrome in TCM. National well-known professor Wang Lvqiu proposed that the key pathogenesis of RA lies in Coldness and Dampness Obstructing Collaterals, he developed experienced formula Bi Tong Ling Powder for early stage of RA with the syndrome type of Collaterals Obstructed by Coldness and Dampness, which was born out to be effective after several decades of clinical practice. Pre-clinical research shows that this formula has the effect of anti-inflammation and immune suppression.Objective:Reviewed the TCM literature for RA and divided the RA into different patterns. Based on the literature reported, RA model was established. The mechanism was study in vitro and in vivo.Method:The literatures were reviewed and the TCM names, etiology, pathological mechanisms were defined and draw a conclusion that cold-damp invading in the interior and obstruction of collaterals by blood stasis were the most important TCM basis. The CIA rats were applied as the model and were treated by the Bitongling granule. The score of the joints, the volume of joint, the edema of joint and pathological findings were analyzed and the expression of VEGF,MMP-3, TNF-α,IL-1βwere analyzed in order to further explained the mechanisms of the BiTongLing particle for RA.Results:Cold and Dampness was always accompanied by Stagnation, cold,dampness and phlegm, which influenced each other and caused the process of the RA persisting very long time. Therefore, dispel cold and removed the dampness, disperse blood stasis and dredge collateral were always used in treatment of RA. BiTongLing particle can decrease the joint edema and prevent the proliferation of synovial membrane and decrease injure of the cartilage. From the rat model, the BiTongLing particle can inhibit the expression of TNF-a and IL-1βin synovial membrane cell primary culture and decrease the expression of VEGF and MMP-3 in synovial membrane.Conclusion:From the study, conclusions were drew as follows:①Cold and dampness are the important risk factor for RA and the cold-damp invading in the interior and obstruction of collaterals by blood stasis were the most important TCM interpretation of the cause. The channel obstruction by cold and dampness are the most common pattern of RA. Dispel cold and removed the dampness, disperse blood stasis and dredge collateral are always used in treatment of RA.②The proliferation of synovial membrane is very active in primary culture cell, as is the most important pathological findings in RA. In RA, the VEGF and MMP-3 can increase the vascular prolifereation and degrade the cartilage and they can be used as the markers of the activity and severity of RA.③BiTongLing particle can decrease the joint edema and prevent the proliferation of synovial membrane and decrease the injure of the cartilage.④BiTongLing particle can decrease the expression of IL-1βand TNF-αin synovial membrane cell primary culture and decrease the proliferation of the synovial membrane, inhibit the vascular growth and prevent the injure of joint.⑤BiTongLing particle can decrease the over-expression of VEGF and MMP-3 in synovial membrane and prevent the proliferation of the synovial membrane, inhibit the vascular growth and prevent the injure of joint.Points of innovation:BiTongLing particle can decrease the expression of IL-1βand TNF-αin synovial membrane cell primary culture and inhibit the over-expression by real-time RT-PCR and the mechanisms of protection of BiTongLing particle for synovial membrane in RA are explained by this sutdy.