Mechanism Of Claudin-1/F-actin On The Effect Of Total Glucosides Of Paeony On Serum LBP In CIA Model Rats

Background and objective: Rheumatoid arthritis(RA)is a systematic autoimmune disease,Lipopolysaccharide binding protein(LBP)is a new sensitive disease activity biomarker for rheumatoid arthritis.Total glucosides of paeony(TGP)are biologically active compounds extracted from the roots of the traditional Chinese herb,Paeonia lactiflora Pall,and now is widely used to treat RA in China.However,the Gastrointestinal adverse effects of total glucosides of paeony are also widely recognized.By reviewing the literature,we hypothesized that the TGP may exert an immunosuppressive effect on RA inflammation through its influence on the intestinal mucosal barrier and mucosal immunity.This study constructed a collagen-induced arthritis(CIA)rat model,detected the concentration of LBP in serum and the expression of claudin-1 / F-actin protein in the intestinal mucosal barrier,for the purpose to verify the above hypothesis and provide experimental evidence for the efficacy and safety of TGP in the treatment of RA.Methods: Forty SD male rats were randomly divided into normal control(n=10)and model group(n=30).The model rats were modeled using bovine type II collagen to replicate the CIA model.After the model was successfully copied,they were randomly divided into the model control group,the TGP group and the methotrexate group.They were administered in groups for 1 week,for a total of 28 days.During the experiment,the general condition,weight change,feces character,and arthritis index of the rats were observed.The knee joint micro CT examination was used to observe the joint lesions.Elisa method was used to detect the serum LBP concentration in rats.The colonic HE staining in rats was observed pathologically and immunohistochemically.Expression of claudin-1 and F-actin protein in rat colon.Statistical analysis was performed on the experimental data using SPSS25.0.Results: 1.TGP can reduce arthritis index in CIA rats and improve the bone destruction of knee joint indicated by micro CT examination.2.TGP can decrease the serum LBP concentration in CIA rats.3.TGP can inhibit necrosis and shedding of colonic epithelial cell,Degenerative necrosis and inflammatory infiltration of the lamina propria,and repair and protect the colonic mucosal barrier in rats.4.TGP can increase the expression of claudin-1 and F-actin protein in intestinal mucosa of CIA rats.Conclusion: Total glucosides of paeony may up-regulate intestinal claudin-1 / F-actin protein expression,lower serum LBP concentration,and then reduce arthritis index in CIA rats,have an effect on relieving arthritis,improving joint bone destruction,and protecting the intestinal mucosal barrier.