Study On The Anti-Rheumatoid Arthritis Effects And Mechanisms Of Shuji Tablets

ObjectivesBased on the inflammation,pain models and adjuvant arthritis model,to study on anti-inflammatory,analgesia and anti-Rheumatoid Arthritis effects and Mechanisms of Shuji tablets.The effect of Shuji Tablets on RA was evaluated,which provided scientific basis for Shuji Tablets to declare national new drugs.MethodsThe research mainly divided into two parts:1.Anti-inflammation and analgesia effects of Shuji tabletsTwo models of acute inflammation of egg white induced rat paw swelling and glacial acetic acid-induced peritoneal capillary permeability,a chronic inflammation model of tampons-induced granulomatoin tumor in rat,to study the anti-inflammatory effects of Shuji Tablets.The toxicity of Shuji Tablets was observed through statistics of the organ status and organ coefficients of experimental animals.Establish mouse hot plate and acetic acid-induced writhing model in mice to study the analgesic effects of Shuji Tablets.2.The Anti-Rheumatoid Arthritis effects and mechanisms of Shuji tabletsEstablish a complete Freund’s adjuvant(CFA)-induced adjuvant arthritis(AA)model in SD rats,observe the effect of Shuji tablets on body weight,awelling of the primary and secondary joints,aeneral condition,arthritis index,number of joint swelling in the limbs,Organ coefficient,pathological changes of ankle joint tissues on the secondary sides of AA model rats.In order to evaluate the basic drug efficacy of Shuji tablets in the treatment of RA.Serum IL-6,IL-1β and TNF-α protein levels were detected by ELISA;PGE2 protein levels in serum and inflamed lateral foot tissues were measured by UV;The content of TLR4,MyD88 and NF-κBp65 protein in the synovial tissue of the secondary ankle joint was measured by immunohistochemistry.In order to study the mechanism of Shuji tablets in the treatment of RA.Results1.Anti-inflammation and analgesia effects of Shuji tablets(1)Anti-inflammatory effect① Egg white induced rat paw swelling:The feet of the model control group swells after cause inflammation(P<0.05),Reach the peak of swelling 0.5h after inflammation.Comparad with the model control group,the swelling degree of paw of Shuji tablets was reduced in all groups(P<0.05),and the swelling degree decreases with time within 0.5～5h.② Glacial acetic acid-induced peritoneal capillary permeability:Comparad with the model control group,The OD of mouse peritoneal inflammatory extracts of Shuji tablets was reduced in all groups(P<0.05).③ tampons-induced granulomatoin tumor in rat:Comparad with the model control group,the dry weight of tampons of rats of Shuji tablets was decreased in all groups(P<0.05).Comparad with the model control group,there was no statistical difference in the organ coefficients of liver,spleen,thymus,and kidney of rats in all groups of Shuji Tablets(P>0.05).(2)The Anti-Rheumatoid Arthritis effects and mechanisms of Shuji tablets The weight of AA model control group rats decreased significantly(P<0.05),Each dose of Shuji Tablets can increase rat weight(P<0.05).Comparad with the model control group.the ankle swelling degree,whole body score,arthritis index score,limb joint swelling number,thymus,spleen,liver,and kidney organ coefficients of Shuji Tablets were significantly reduced(P<0.05).Serum IL-6 levels reduced Significantly(P<0.05),Serum TNF-α and IL-1β levels in Shuji Pian high and middle dose groups were significantly reduced(P<0.05).The PGE2 content in the ankle joint tissue and serum of the inflammatory side of the rat reduced Significantly(P<0.05).Immunohistochemical staining results showed that TLR4,MyD88,and NF-κBp65 protein staining in ankle joints and synovial tissues of AA model rats increased significantly,showing a dark yellow-brown color.Shuji tablets can reduce TLR4,MyD88,NF-κBp65 protein staining in rat ankle and synovial tissue,making the color lighter.Conclus ions(1)Shuji Tablets can significantly inhibit the swelling of rats’feet caused by egg white,acetic acid induced increased capillary permeability in mice,cCotton ball granulation.It suggests that Shuji Tablets can inhibit acute and chronic inflammatory swelling and proliferation.(2)Shuji Tablets can increase pain threshold in hot plate mice,reduce the number of writhing in mice caused by acetic acid.It suggests that Shuji Tablets can inhibitheat-stimulated pain and inflammatory pain.(3)AA model can simulate the symptoms of clinical RA patients.Some symptoms of the AA model are swelling of the joints of the extremities,systemic inflammatory response,immune organs and liver and kidney enlargement,abnormal expression of inflammatory factors IL-6,TNF-α,IL-1β,PGE2,TLR4,MyD88,NF-κBp65.(4)Shuji Tablets can improve weight and physical function of AA model rats,relieve swelling of the ankle joint and systemic inflammation.Shuji Tablets can reduces spleen and thymus immune organs and liver and kidney organ coefficients.Shuji Tablets can reduce the levels of inflammatory factors IL-6,TNF-α,IL-1β,and PGE2,simultaneously reduce the protein levels of TLR4,MyD88,NF-κBp65 in the ankle synovial tissue,improve the inflammatory infiltration and proliferation of synovial tissue,and thereby delay joint cartilage and lesions or joint deformities.It is suggested that the mechanism of Shuji Tablets in the treatment of RA may be related to the inhibition of TLR4/NFκB signaling pathway.