| Objective:Rheumatoid arthritis(RA), with high morbidity, is a kind of systemic autoimmune disease which mainly involved peripheral joints, Rheumatoid arthritis distributed around the world,which’s prevalence in different population is 0.18%-1.07%, the total number of patients with rheumatoid arthritis in our country is more than 500 million. The pathogenesis of RA has been evolving for half century. RA has a series of important pathological changes, including chronic symmetric synovial inflammation, angiogenesis forming pannus and destruction of cartilage, finaly joint malformation lead to defuctionalization. studies have confirmed that Monocyte-macrophages and lymphocytes infiltrated in synovial tissues produce large amounts of cytokines, these cytokines by acting on multiple cells and mutual adjustment, to form a complex network, and eventually lead to the occurrence and development. It has been a hot research for searching effective target to inhibiting angiogenesis and synovial inflammation. Biqi Capsule(BIQI.BQ) has the function of nourishing qi and blood, expelling wind and removing dampness, promoting blood circulation and relieving pain, which has a good effect on muscle and joint pain, joint stiffness and deformation. The effective of BQ on RA synovial joint synovitis and pannus has not been reported.In Synovial inflammation and pannus generate. In this study, a rat model of Ⅱ collagen-induced arthritis(CIA) was replicated to Simulate the pathogenesis of RA. We discussed the possible mechanism of BQ by observing the CIA arthritis rats’ pathological changes in synovial and detecting the expression of osteopontin(OPN), interleukin-18(IL-18),angiopoietin-1(Ang-1), tumor necrosis factor-a(TNF- a) to provide the new experimental evidence of BQ for the clinical treatment.Methods:1.Feeding SD female rats, bovine type II collagen and incomplete Freund’s adjuvant1: 1 mixture was given subcutaneously twice a week apart to established collagen-induced arthritis model in rats.2. first, 55 SD female rats were randomly divided into model group45 and the normal group 10. Screened successful model rats 42,and then randomized block divided by paw swelling: model group10, high dose BQ group10, middle dose BQgroup10, middle dose MTX group12. Two weeks after the initial immunization we began the treatment for 4 weeks by filling the stomach.3. Dynamic observation of the mental state,weight, activity and other behavioral changes. of each group rats.4. From the initial immunization, every other day rats’ ankle volume was measured with drainage method to observe the changes of Joint swelling.5.After four weeks treatment, the rats were killed by Femoral artery bloodletting. rats’ serum IL-18, TNF-a,OPN,Ang-1 content was tested by elisa,the expression of IL-18,OPN,Ang-1 which in the synovial tissue was detected with Immunohistochemical staining method. HE staining was used to examine the pathological changes and angiogenesis in joint synovium of the rats.Results:1. CIA model rats success rate is 93.3﹪(42/45):Based on the TNF-a level of serum and the joint swelling symptoms,we confirmed that the CIA model was successfully builded.2. Joint swelling degree: CIA rat hind limb swelling began to appear on the 11 th day,and on the 15 th day reach the top. During the first three weeks,middle dose BQgroup and middle dose MTX group Swelling fade faster than high dose BQgroup. In the fourth week,all the three treatment groups’ swelling were apparently subsided and the model group swelling subsided slowly. After 4 weeks treatment, hind limb swelling degree of the three treatment groups was significantly lower than model group, the difference was statistically significant.3. HE pathological evaluation of ankle joints: Three treatment group rats’ joint synovial proliferation and inflammatory cells infiltration degree was lower than model group, the difference was statistically significant. And the middle dose BQ group’s effect was more obvious, neutrophils, lymphocytes, plasma cells were all significantly reduced..4. Synovial angiogenesis situation: model group’s synovial angiogenesis increased significantly, Vessel lumen was expanding and congestive, with a lot inflammatory cells accumulation. The angiogenesis of three treatment groups was relaxed much more obvious than model group, the difference was statistically significant. The MVD values of middle dose BQ group are lower than the other two treatment groups’, the difference is statistically significant.5. Each serum cytokine levels: Model group, serum cytokine TNF-α, IL-18, OPN,Ang-1 levels were significantly increased, and three treatment groups’ cytokine levels have decreased comparing with the model group, the difference is statistically significant. Middle dose BQ reduced IL-18、Ang-1 serum level more significantly than the other two treatment group, the difference is statistically significant.6. Synovial tissue expression of various cytokines: Model group rats’ synovial tissue cytokine IL-18, OPN, Ang-1 levels were significantly increased. Three treatment groups compared with the model group, every cytokine expression were reduced,the difference is statistically significant. Middle dose BQ can reduce IL-18 expression which is more significant than high dose BQ, middle dose BQ also can reduce Ang-1expression and which is better than middle dose MTX, the two differences are all statistically significant. The comparison between every two treatments about synovial OPN expression is not tatistically significant.Conclusion:By analyzing the experimental results, we know that BQ has effective in treating CIA rats. Both high and middle dose BQ can reduce CIA rats’ joint swelling degree、inhibit hyperplasia and angiogenesis of synovial. BQ can reduce CIA rats serum TNF-α, IL-18, OPN, Ang-1 level and reduce the expression of synovial IL-18, OPN, Ang-1. Therefore, we speculate that BQ takes the therapeutic effective probably by reducing serum and synovial TNF-α, IL-18, OPN, Ang-1level. Different dose has different effect of the treatment, Correct and reasonable doses can enhance the clinical efficacy and reduce the side effects of the drug.The therapeutic efficacy on CIA rats of BQ is clear, but its basic and clinical research still needs further improvement. |
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