Investigation on the Inhibitory Effect of Methotrexate on Rheumatoid Synovitis via the TLR4-NF-κB Pathway in a Rat Model.

Abstract

Rheumatoid arthritis (RA) is a rheumatoid immune system disease characterized by joint inflammation, resulting in synovial hyperplasia, articular cartilage damage or distortion, and extra-articular involvement. The morbidity is higher and the treatments are not effective in clinical, and also no unified to the pathogenesis of such diseases. The aim of this paper is to establish a rat model of rheumatoid synovitis and observe the inhibitory effect of methotrexate on this disease. A total of 100 SD rats are selected and randomly divided into 5 groups, with 20 rats in each group. The cold and damp factors of rheumatoid arthritis are induced by cold water and the arthritis score is used to verify the model. ELISA is used to measure the protein expression of Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB) and inflammation-related factors, and SPSS25.0 is used for statistical analysis. The results show that there is no significant difference in inflammatory scores among the four groups except the control group. However, after 3 months of intervention, the inflammatory scores in the methotrexate groups are significantly lower than those in the model group, and in the methotrexate group, the higher the dose, the lower the inflammatory scores. The experimental results show that the messenger ribonucleic acid (mRNA) and protein expressions of TLR4 and NF-κB from high to low are in the order of model group > low dose > middle dose > high dose > control group, and the expression trend of inflammation-related factors is the same as mentioned above. These results indicate that methotrexate can repair rheumatoid synovitis by inhibiting the inflammatory signaling pathway TLR4-NF-κB.