| Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease characterized by infiltration of inflammatory cells, proliferation of synovial pannus and generation of synovial tissue. If not accept systemic therapy in early stage of the disease, patients will eventually suffer from destruction of articular cartilage and bone, even bear the joint deformity and loss of ability to work, seriously affecting the quality of life of patients. Pathogenesis of RA can be seen at any age, but postmenopausal women get a higher incidence. And the quantity of female is3times to the male. Currently the worldwide prevalence is about1%, and incidence rate in China is about0.3-0.5%. In traditional Chinese medicine, the disease can be called Wangbi,Wanbi or Lijie, which can damage the tendons, flesh and bone.Synovitis in RA patients is particularly prominent, which resulting severe synovial hyperplasia, causing bone and joint erosion by synovial tissue. The whole process requires large amounts of oxygen and nutrient supply, when the original blood vessels cannot bring in the acquired oxygen and nutritions, in order to increase joint local blood flow, there engendering newborn blood vessels and vascular tissues. So pathological angiogenesis is an important link in the pathogenesis of RAWe carried out a long-term system of clinical and experimental research of Chinese medicine treatment of RA in Guang An Men Hospital of China Academy of Traditional Chinese Medicine, from which we summarize the key pathogenesis of active RA as heat-dampness and blood stagnation " and proposed " clearing heat-dampness and activating blood " as treatment of the fundamental law. From the clinical studies we found that, taking the proposed "Heat Clearing and Blood Circulation Activating Decoction" can relief clinical symptoms and improve joint function in RA patients. Even it can improve Sharp score in1-year,3-year period. Experimental studies show that taking "Heat Clearing and Blood Circulation Activating Decoction" can increase the IL-4content of local synovial tissue and serum of CIA rats, also can inhibit the expression of INF-y, and maintain the balance of Thl/Th2cells; the contents of IL-17, MIP-1α and RANKL in serum were decreased, suggesting that the prescription can retard bone destructioa Base on the previous researches, we move forward a single step to investigate the mechanism of activating the blood circulation of the decoction.Objective:To investigate the "blood-activating" effect of "Heat Clearing and Blood Circulation Activating Decoction", revealing how the herbs inhibit angiogenesis in synovial tissue, to provide theoretical and experimental support for the treatment of active RA. Methods:We take CIA rats model, treated with "Heat Clearing and Blood Circulation Activating Decoction" large and small doses of the intervention, compared with normal control group, model control group, positive drug (LY294002) control group, observing the rat paw swelling, pathological section of the ankle joints and synovial tissue, inflammatory cytokines (INF-y), stasis associated factor (tPA) and angiogenic factors (eNOS, VEGF), including cytokines were detected by ELIS A.Results:Taking "Heat Clearing and Blood Circulation Activating Decoction", the swollen joints of CIA rats got alleviated; joint pathology examination showed the decoction may inhibit synovial hyperplasia, delaying the destruction of articular cartilage and bone; synovial pathological sections showed that, treated with the prescription, inflammatory cells in synovial tissue were significantly reduced compared with the model group, and the number of blood vessels visible decreased significantly; detection of cytokines:treated with the decoction, INF-y level expressed in serum was decreased significantly compared with the model group (P<0.05); it also can reduce the generation of tPA when treated with high-dose group(P<0.05); compared with model group the expression of eNOS was down regulated in low-dose group(P<0.05), and it was significantly inhibitted in high-dose group (P<0.01); for VEGF regulation, the decoction can reduce its expression, but not statistically significant (P>0.05).Conclusions:Taking "Heat Clearing and Blood Circulation Activating Decoction" can effectively control joint inflammation, retard destruction of the articular cartilage and bone, reduce synovial proliferation, also can improve blood stasis in the joints, even can reduce the number of new blood vessels, which confirms the "blood-activing" effect of the decoction. But the regulation to VEGF is not obvious; probably it is associated with the sampling time, which need for follow-up experiments to confirm. |
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