| Objective: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory disorder and progressive joint destruction. Moreover, vascular endothelial growth factor (VEGF) is related to the hyperplasia of blood vessel. Treatment of rheumatoid arthritis (RA) with Bikangyin Mixture (BKY) decoction is highly clinically effective. This study was undertaken to investigate the clinical efficacy of Bikangyin decoction to the patient in active stage of rheumatoid arthritis (RA), explore the precise mechanism of the action of BKY in RA, and provide the experimental evidence for its application. Methods: 1 Arthritis model in rats induced by type II collagen was established. 2 The feet swelling degrees of rats were measured, and then calculated the swelling rate. 3. After a short-term treatment, the synovial histopathology of rats was observed with optical microscope respectively. 4 Immuno -histochemistry techniques have been used to detect T-cell subsets, cytokines TNF-α,TGF-β,MMP3,TIMP1 and VEGF in synovial tissue (synovial membrane) of CIA rats. The above results were analyzed with image analysis system. Result: 1 The CIA rats had obvious and persistent arthrocele, but the articulus had no clinical manifestation of red glow. The histopothology of arthral tissue showed lymphocyte infiltrating and liner hyperplasy in the synovial membrane, neovascularity and pannus'forming. 2 The BKY decoction of high dose had more obvious effects than low-dose BKY decoction or MTX on reducing foot swelling or arthritis index. 3 There were a great quantity of lymphocyte infiltrating and synoviocyte hyperplasy in the model group rats'synovial tissue, but the situation was well in the BKY decoction high-dose group. 4 The number of chondrocytes with positive TNF-αexpression was lower and the chondrocytes were stained lighter in normal group than those in model group and low-dose MTX group(P <0.01). The expression of TNF-αin high-dose and low-dose TBL groups and high-dose RTW group was similar to that in normal group and more obvious than that in high-dose and low-dose MTX group(P<0.05) and model group(P<0.01).The expression of TGF-βin normal group was more obvious than that in high-dose and low-dose RTW groups(P<0.05).The expressions of TNF-αand TGF-βin high-dose and low-dose TBL groups were similar to those in normal group and different from those in model group(P<0.01). 5 The expression of VEGF in high-dose group was lower than that in normal group or other group (P<0.05). 6 In the high-dose group, the expression of MMP3 dropped, but the expression of TIMP1 rose. 7 The X-ray imaging changes of CIA rats: The ratsof model group had soft tissue swelling,destruction of bone and vague joint space. That situation changed a lot after treating with high dose BKY decoction, but the changes were little in the low-dose group or MTX group. Conclusion: The detection result of cytokine by immunohitochemistry showed that Bikangyin decoction has obvious effect to arthritis induced by type II collagen. The mechanism of its action are mainly: First, it can reduce the expression of TNF-αand raise the expression of TGF-β, and then keep the balance of Th1/Th2,control the hyperplasy of synoviocyte,lighten arthral inflammatory,prevent the cartilage or bone from destruction. Second, it can inhibit the generation of VEGF, and so inhibit vascular proliferation,pannus forming; Reduce vasopermeability; stop the excess hyperplasy of synoviocyte; prevent or lessen the destruction of bone. Lastly, it can inhibit the excess expression of MMP3 and adjust the balance of MMP3/TIMP1, and so relief the symptom of arthritis and the destruction of cartilage.
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