| Background:Rheumatoid Arthritis (RA) is a kind of non-infectious inflammation autoimmune disease; its main clinical manifestations are joint pain, stiffness, deformity and functional disorders. The specific symptoms of RA is the polyarthritis of the hands, wrist and foot joint symmetry and it can also happened in knee, hip and other large joints. The etiology of RA is so far unknown, and it is still a refractory disease, the rate of misdiagnosis and irrational drugs using rate are very high, and it is still no specific effective therapy and drugs for this disease till today. Chinese medicine treatment has certain advantages in curing RA because of its fewer side effects and pain relief, improves the quality of life in patients with good results.Rationale of Research:Synovitis is the basic pathological manifestations of RA; Toll like Receptor (TLR) is a series of important receptor which exist in cell-mediated inflammatory mediators, whose dominant cell signaling pathway plays a key role in defense for the host, especially as the bridge linking the innate immunity and acquired immunity. However, the overexpression and activation of TLR will lead to severe immune dysfunction. Nowadays, People have done a lot of studies which have shown that the onset and progress of the abnormal TLR activation mediated inflammatory response plays a very important role in RA, especially the occurrence and development of synovitis.Objectives:RA had been recognized by the great medical scientist in ancient China Zhangzhongjing in thousands of years ago as the name of "Lijie" disease. He had also developed a famous decoction named Guizhishaoyaozhimu Decoction for the diease, which is still guiding clinical practice.Methods:Reviewed the TCM literature for RA and divided the RA into different patterns. Based on the literature reported, to invest the way of curing RA by the decoction and method developed by Zhangzhongjing. RA model was established. The mechanism was study in vitro and in vivo. The literatures were reviewed and the TCM names, etiology? Pathological mechanisms were defined. The CIA rats were applied as the model and were treated by the Guizhishaoyaozhimu Decoction. The score of the joints, the volume of the joints, the edema of joint and pathological findings were analyzed and the expression of IL-1, IL-6, IL-17, TNF-α,NF-κB, MyD88, TLR2, TLR4, TLR9, SIGIRR were analyzed in order to further explained the mechanisms of the Guizhishaoyaozhimu Decoction by the way of SP-immunohistochemical, ELISA, Western-blot and PCR.Results:The experiments showed that Guizhishaoyaozhimu decoction has the certain inhibition on the joint swelling of CIA rats, and different dose of group of Guizhishaoyaozhimu decoction all shows their ability of inhibiting the expression of TLR2, TLR4, TLR9, MyD88, NF-κB, IL-1, IL-6, IL-17, TNF-α, and the ability of raise the expression of SIGIRR.Conclusion:①Guishaozhimu decoction can be used by solving RA.②Guishaozhimu decoction can significantly reduce paw swelling, joint score and joint histopathological changes of CIA rats.③Toll-like receptor signal pathways is related to the happening and developing of RA.④Guishaozhimu decoction might can relieve the inflammation of RA by inhibiting the Toll-like receptor signal pathways.⑤The suppression of negative regulator of Toll-like receptor signal pathways may induce the happening and developing of RA.⑥Guishaozhimu decoction might can relieve the inflammation of RA by activate the expression of the negative regulator (SIGIRR) of Toll-like receptor signal pathways.Points of innovation:The research had Used different methods to the observe the expressions of IL-1, IL-6, IL-17, TNF-α,NF-κB, MyD88, TLR2, TLR4, TLR9and SIGIRR by different way of SP-immunohistochemical, ELISA, PCR and Western-blot. The indicators which had been detected covered many different part of the toll-like receptor signal pathways. |
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