| Background and purpose: Rheumatoid arthritis(RA) is a synovial hyperplasia,cartilage and bone destruction of the pathologic characteristics of autoimmune disease,mainly with chronic inflammation of the synovial membrane, multiple joint swelling,pain and cause the ankylosis, or even loss of function in clinical manifestations.The etiology and pathogenesis is still unknown.But studies show that RA synovial tissue were infiltrating inflammatory cells, cytokines produced by a variety of cells and act on mutual adjustment, through complex relationships, and finally resulted in the development and progression of rheumatoid arthritis.Experiments have proved that in the pathogenesis of RA, TNF-a and IL-1? are two most important terminal inflammatory cytokines, which TNF-a not only through NF-?B, JAK / STAT pathway mediated RA synovium erosion reaction, but also induce synovial cells produced a large number of inflammatory cytokines, such as IL-1, IL-8, participate in RA synovium erosion reaction. Many studies have shown that the biological effects of these inflammatory cytokines can be slowed down by biological technology, which can reduce inflammation and improve clinical symptoms. Therefore,TNF-a receptor antagonist etanrcept,infliximab and IL-1 receptor antagonist anakinra as the representative of biological pharmaceutical preparations, are expected to bring new hope to RA patients. But the biological agent is expensive and the biological safety still needs to be confirmed in clinical trials, so it has not been used in a large scale.Also the current standard therapy for RA including non steroid body anti-inflammatory drugs and disease-modifyinganti-rheumatic drugs can not improve the symptoms of patients with long-term and have strong secondary action. Therefore,looking for new drugs to improve the RA condition remains a clinical challenge.Photodynamic therapy has been widely used in the treatment of tumors, RA inflammatory synovial active growth and metabolism, similar to tumor tissue.Previous experiments have proved that cultured synovial cells can rapidly absorb the photosensitizer hypericin, PDT on synovial cells have obvious killing effect. Thisstudy on the basis of previous experiments, by using the animal model of rheumatoid arthritis, carried out the following studies:(1) understanding therapeutic effect of hypericin-PDT on rheumatoid arthritis model;(2) preliminary exploration of the mechanism of this effect.Observe the effect of traditional Chinese medicine photosensitizer hypericin of collagen II-induced arthritis models(CIA)mice joint swelling, arthritis index and histopathological changes in the ankle joint.Determine the therapeutic effect of hypericin mediated photodynamic therapy on CIA mice, and to investigate the effects of hypericin mediated photodynamic therapy on serum TNF-a and IL-1 expression levels and explore the potential mechanism of hypericin mediated photodynamic therapy for the treatment of RA.Method: collagen II were dissolved in 0.1 mol/L glacial acetic acid, then and equivalent completely Freund's adjuvant emulsified, in C57BL/6 mice tail root intradermal injection of 0.1 ml, 21 d after repeated injection of the same amount of emulsifier for strengthen immunity, to establish the CIA mice.The successful model of the mice were randomly divided into model group,methotrexate group and hypericin high and low dose treatment group, unimmunized mouse in the normal control group; From the twenty-eighth day after the first immunization, normal control group and model control group were given intraperitoneal injection of normal saline, not given medication, Hypericin high-dose treatment group were given within the plantar intradermal injection at a concentration of 20?/mol hypericin, hypericin low dose treatment group were given within the plantar intradermal injection at a concentration of 10?/mol hypericin, methotrexate group were given intraperitoneal injection of methotrexate injection, 3.6mg/kg, Once a week for 4weeks, Dynamic observation of changes in the indications of mice weight,hind foot ankle swelling, and arthritis index etc; In 3 hours after the last treatment, the mice were killed from each group after ankle joint, he staining to observe; mice serum was collected and enzyme-linked immunosorbent adsorption method(ELISA) to detect TNF-a and IL-1? content.Results: Compared with normal mice and model mice hind foot joint swelling significantly, with claudication, hind foot joint swelling and arthritis index increased significantly, serum TNF-a and IL-1 levels were also significantly elevated(P <0.05);With the model group, the treatment group mice foot swelling of joints reduce,degree of movement, hind foot joint swelling degree, joint arthritis index and serum TNF alpha, IL-1 beta level were significantly decreased(P < 0.05);the high dose of hypericin treatment group compared with the other two groups, hind foot joint swelling and arthritis index and serum TNF- alpha and IL-1 beta levels were decreased has remarkably statistical difference( p < 0.05); The HE staining of model group showed that the hind ankle joint was obvious inflammatory cell infiltration,synovial cell hyperplasia was observed in the destruction of articular cartilage, joint deformity; compared with the model group, each drug Group of inflammatory cell infiltration, proliferation of synovial cells, destruction of the articular cartilage,pannus formation were reduced;hypericin high dose treatment group and the other two medication group, inflammatory cell infiltration and hyperplasia of synovial membrane less, articular cartilage and bone destruction, deformity extent lighter.Conclusion: hypericin mediated photodynamic therapy on rheumatoid arthritis model of CIA mice joint swelling has significantly reduced, but also improve joint synovium,Cartilage Pathological Morphology and its mechanism of action may through by inhibition of inflammatory cytokine TNF-a and IL-1? and to achieve anti-inflammatory swelling of joint protection. |
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