Therapeutical Effects And Mechanism Of Bikangyin Mixture On Collagen-induced Arthritis In Rats

Objective: Rheumatoid arthritis(RA) is a chronic, systemic disorder that is characterized by a symmetric polyarthritis finally leading to progressive joint destruction. The basic tissue change of RA are joint inflammation, proliferation of synovial cell, and synovial fibre invading synovial cartilage and bone. Although the aetiology of RA remains undefined, many data suggests that T lymphocytes, macrophage and proliferating synovial cells are very likely to play a major role in the pathogenesis of this disease. In particular, cytokine produced by these cells appear to be critically involved in the intiation and perpetuation of RA. As the important medium of synonitis inflammatory reaction and immune response, cytokines which can promote or suppress inflammation and have the positive or degenerative action of immunological regulation participates the whole process of membrana synovialis pathological changes. the disturbance of cytokines network scilicet the imbalance between proinflammatory cytokine (such as IL-1,TNF-α) and anti-inflammatory cytokine (such as IL-4,IL-10) plays an exceedingly role in the pathogenesy of rheumatoid arthritis. In this study, we will establish a experimental collagen-induced arthritis, observe Bikangyin Mixture(BKY) regulative effect on proinflammation cytokine (IL-1β,TNF-α) and anti-inflammation cytokine (IL-4,IL-l0), explore the immune mechanism of treatment rheumatoid arthritis with Bikangyin Mixture. Methods: CIA rat model was established by subcutaneouly injecting bovine nasal cartilage II collagen (BIIC). The rats were randomly divided into four groups, Normal group, BKY high dose group, BKY low dose group, Methotrexat treat group,CIA control group. The hindpaw volumes, the arthritic index, the pathological score and the radiographic changes of all rats were compared separately, serum level of TNF-α,IL-1βand IL-4,IL-10 were assayed by enzyme linked immunosorbent assay (ELISA) also. Results: 1.Arthritis in rats took place in 9-20 days after the primary immunization. The symptoms included such as: redness and swelling of the joints, limited joint movement. Pathologys indicated synovium hyperplasia and inflammatory cell infiltrations, formation of lymphatic nodule-like structure and pannus, erosion of articular cartilage and subchondral bone. Soft-tissue swelling,bone erosion, narrow of the joint cavity even articular bone fusion were demonstrated by the radiography. 2.All the treat group can improve the arthritis symptoms and decrease the mean of arthritis scores in CIA rats different extent compared with CIA control group, the effects of controlling arthritic symptom and cartilage with subchondral bone's erosion were equal nearly among the Bikangyin Mixture groups and the MTX treat group by the radiography andPathology observation. But the ALT level of MTX treat group increases obviously than other treat groups, liver cell degenerescence appearced by pathology observation, while the rats of BKY high and low dose group were normal. 3. Bikangyin Mixture groups(Both BKY high and low dose group) can suppressed the abnormal high Serum levels of IL-1β,TNF-α, meanwhile upgrade the Serum low levels of IL-4 and IL-10 in CIA rats after the treatment of six weeks. Conclusion: 1.Therapeutical effects to CIA rats of Bikangyin Mixture are equals to MTX, but its adverse reaction is smaller than that of MTX, so Bikangyin Mixture can be safe used to the clinical of RA. 2.Its mechanism maybe related to the modification of the abnormal immunological function of CIA rat by suppressed the abnormal high serum levels of IL-1β,TNF-α, upgrade the serum levels of IL-4 and IL-10 in CIA rat,recover the balance of cytokine network.