| Background： Rheumatoid Arthritis (Rheumatoid arthritis, RA) is a chronicdestructive multi-joint disease, is a by the antigen-driven, multi associated with geneticfactors involved in autoimmune diseases, the incidence of infections and mainly around thecentral link autoimmune reactions, RA with multiple joint swelling and chronic pain as themain clinical manifestations, causes chronic arthritis synovial hyperplasia, cartilagedegradation and bone destruction is an important pathological features. Toll-like receptors(Toll-like recepter, TLR) family in the autoimmune and inflammatory diseases play animportant role. TLRs mainly expressed in macrophages and dendritic cells, directlyinvolved in the innate immune response and to identify relevant pathogens through TLRsstimulate expression of pro-inflammatory cytokines and costimulatory molecules increases,and thus participate in the adaptive immune response. Myeloid differentiation factor88bythe TLRs (TLR3exception) activation, TLRs signal transduction pathway is the mostimportant adapter protein. MyD88innate immune response in the boot and adaptiveimmune responses have an essential role. Existing studies have shown that TLRs in thepathogenesis and progression of rheumatoid arthritis play an important role, and myeloiddifferentiation factor MYD88TLRs pathway as a core protein in the pathogenesis ofrheumatoid arthritis, the role has become more prominent. Chinese acutum asMenispermaceous ivy plant ivy and hair dry cane, bitter, flat, liver, spleen, withrheumatism, meridian, analgesic efficacy for the treatment of rheumatism, joint swellingpain. Sinomenine(Sinomenine,8-didehydro-4-hydroxy-3,-dime-thoxy-17-methylmorphinan-6-one,C19H23NO4) from the Chinese acutum alkaloid extracted monomer having Sinomeninecertain anti-inflammatory, immune suppression, pain, inhibit cartilage destruction such asthe role of plants in a very strong histamine releasing agent widely used in the clinicaltreatment of rheumatoid arthritis. A variety of inflammatory cytokines involved in theonset and progression of RA, such as TNFα, IL-1, IL-6and other pro-inflammatorycytokines, can participate in immune cell activation and induction of metalloproteinaseproduction, promote joint destruction. The results show that SN improvement in RAsynovial pathology. Since SN can be reduced in rats with adjuvant arthritis synovialinflammatory cytokine expression and inhibition of human synovial cells in T cellactivation and proliferation, and not only in the promotion of MyD88overexpression ofinflammatory cytokines play an important role in promoting a more T cell proliferation andstart the adaptive immune response. SN discovered in the early anti-inflammatory effect onsynovial cells on the basis, we propose: SN synovitis in RA patients can inhibit cytokineexpression and inhibition of T cell-induced adaptive immune response, the specificmechanism may be related to inhibition MyD88pathway activation, lowered itsdownstream related factors over expression. Therefore, we used rat model of adjuvantarthritis in experimental design, experimental rats were observed SN joint pain,inflammation, synovial pathology, synovitis cytokines TNFα expression; while sliding on rats observed SN MyD88film effects. SN provides for the treatment of RA animalexperimental basis.Objective: In recent years, the effects of the myeloid differentiation factor88（MyD88）on the pathogenesis and progression of rheumatoid arthritis attract more andmore attentions. The role of sinomenine in the treatment of rheumatoid arthritis is alsomore and more recognized. In this experiment, we study the effect of sinomenine on thejoint pain, synovial pathological changes and synovitis in rat adjuvant-induced arthritis andthe effect of sinomenine on MyD88expression. We further investigate the therapeuticeffect of sinomenine on rheumatoid arthritis and its specific mechanisms.Method：1. A total of40male Sprague-Dawley rats were randomly devided into4groups (the normal group, the model group, the sinomenine group and the methotrexategroup), with10rats in each group. In addition to the normal group, the rats in the othergroups were injected with complete Freund’s adjuvant into the plantar surface of right hindpaw to induce adjuvant arthritis. To observe the changes of joint pain in rats before andafter the modeling and drug treatment, we measured the rat behavioral characteristics ondays8,16,24and30.All rats were sacrificed on days30and their synovial tissues wereremoved.2. The HE staining was performed to examine the synovial pathology.3.Theexpression of TNFαin rat synovial tissues was detected by ELISA.4.The expression anddistribution of MyD88were analyzed by western blot and immunohistochemistry.Result：1. The effect of sinomenine on rat heat and mechanical pain.（1）Heat pain:in the8th and16th days, thermal pain threshold of the rats in normal group wassignificantly different from that in other groups. Compared with the model group, thermalpain threshold of the rats in the sinomenine and methotrexate groups had no obviousdifference. And in the24th and30th days, compared with the model rats, the painthreshold decreased significantly in the sinomenine and methotrexate group.(2)Mechanical pain：In the8th day, the mechanical pain threshold of rats in normal group wassignificantly different from other groups. There was no difference between the othergroups.In the16th day, the mechanical pain threshold of the normal group rats were stillmarkedly higher than others. Compared with the model group, the mechanical painthreshold of the methotrexate group decreased significantly. In the30th day, comparedwith model group, the mechanical pain threshold of rats in sinomenine and methotrexate group still reduced significantly.2. The effect of sinomenine on the synovial pathologychanges of rat adjuvant-induced arthritis. The pathological pictures display that comparedwith the normal group, the synovial proliferation and inflammatory cell infiltration in themodel group increased significantly. Compared the model group, the synovial proliferationand inflammatory cell infiltration were improved in the sinomenine group and themethotrexate group.3. The effect of sinomenine on the expression of TNFα in the synovialtissues of the adjuvant-induced arthritis rats. The expression of TNFα in the model groupwas statistically higher than that in the normal group. Compared with the model group, theTNF-α expression in the sinomenine and the methotrexate group were markedly decreased.4. The effects of sinomenine on the expression of MyD88in the synovial tissues of theadjuvant-induced arthritis rats.(1) The expression level of MyD88was analysised in thesynovium of rats by Western Blot. The data show that sinomenine significantly reduce theexpression of MyD88in the synovial tissues of the adjuvant-induced arthritis rats.(2)Immunohistochemistry staining showed that compared with the normal group, the MyD88staining increased significantly. The staining was mainly located in the inflammatory cellsand the staining was dark. Sinomenine decreased the MyD88staining in the synovialtissues of the adjuvant-induced arthritis rats.Conclusion:1. Sinomenine can improve jiont pain of adjuvant arthritis rats.2.Sinomenine can alleviate inflammatory cells infiltration and synovial cell proliferation inthe synovial tissues of adjuvant arthritis rats.3. Sinomenine can inhibit the expression ofTNF-α in the synovial tissues of adjuvant arthritis rats.4. MyD88is highly expressed inthe synovial tissues of adjuvant arthritis rats and sinomenine can decrease MyD88expression.5. Sinomenine has a positive therapeutic role in adjuvant arthritis rats. Themechanism may be associated with decreasing the expression of MyD88in the synovialtissues of adjuvant arthritis rats, which may further inhibit expression of inflammatorycytokines. |
PDF Full Text Request