Abstract:Objective:To investigate the effect of resveratrol on rheumatoid arthritis and study the remodeling of intestinal flora and its mechanism. Methods: DBA/1 male mice were selected as the experimental object. The mouse model of rheumatoid arthritis(collagen induced arthritis,CIA) was induced by subcutaneous injection of the mixture of type II collagen and Freund's incomplete adjuvant at the tail root. The successfully induced mice were randomly divided into CIA model group,CIA+methotrexate group,CIA+resveratrol low-dose intervention group and CIA+resveratrol high-dose intervention group,with 10 mice in each group. On the 21st day of modeling,different doses of resveratrol[2,0.5 g/(kg·d)] were given by gavage,the control group was given the same amount of 0.9% sodium chloride solution,and the methotrexate group was given 0.5 g/(kg·d) for 21 days. The degree of joint inflammation in mice was scored by arthritis index scoring method, the degree of joint damage was evaluated by hematoxylin eosin staining(HE),and the pathological changes of joint tissues in each group were observed. Mouse serum was extracted and tumor necrosis factor- α (TNF- α ) was detected by enzyme-linked immunosorbent assay(ELISA) 、interleukin-6(IL-6) and interleukin-1β(IL-1β). Flow cytometry was used to detect spleen Treg cells(Treg) and helper T cells 17(Th17) on day 42 of immunized mice and CD8 + T cells; the microbial genomic DNA was extracted from the fecal samples of mice on the 42nd day of immunization, and the abundance of Bacteroides,Lactobacillus,Bifidobacterium and Actinomycetes was quantitatively analyzed by real time PCR(RT-PCR);the correlation between the structural difference of intestinal flora and T cells was analyzed,and the regulation of intestinal flora on Th17/Treg balance was clarified. Results:Compared with CIA model group,CIA + resveratrol high and low dose groups can reduce the expression of serum inflammatory factor TNF-α、IL-6 and IL-1β in CIA mice(P<0.01),the high-dose group was more significant. Pathological examination showed that high-dose resveratrol could significantly improve the joint lesions of CIA mice. RT- PCR showed that resveratrol could promote the growth of Bacteroides and Bifidobacteria. Flow cytometry and correlation analysis confirmed that resveratrol could reshape the intestinal flora and restore the balance between Th17/ Treg cells of CIA mice. Conclusion:Resveratrol can increase the growth of Bacteroides,Lactobacillus and Bifidobacterium can effectively improve the related symptoms of CIA model mice.