MiR-146a alleviates inflammation of acute gouty arthritis rats through TLR4/MyD88 signal transduction pathway.

Abstract

The aim of this study was to explore the effect of micro-ribonucleic acid (miR)-146a on acute gouty arthritis rats through Toll-like receptor-4/myeloid differentiation factor 88 (TLR4/MyD88) signal transduction pathway. A total of 30 clean-grade Sprague-Dawley rats were divided into three groups, including agomiR-146a group (n=10), antagomiR-146a group (n=10) and negative control group (NC, n=10). The model was successfully established via a one-time injection of sodium urate into ankle joint cavity. Subsequently, agomiR-146a (10 μL), antagomiR-146a (10 μL) and normal saline (10 μL) were intrathecally injected into rats in the three groups at 1 h before injection and 12 h, 24 h, 48 h and 72 h after injection, respectively. The ankle joint swelling index, joint dysfunction index and joint inflammation index of rats in the three groups were closely monitored. After 72 h of observation, the rats were euthanized, and synovial tissues were collected from the knee joint. The expression and distribution of nuclear factor-κB (NF-κB) in synovial tissues were detected using the immunohistochemical method. Meanwhile, the expression levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay. Furthermore, the mRNA and protein expression levels of TLR4 and MyD88 were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively. No statistically significant differences in the joint swelling index, joint dysfunction index, joint inflammation index, TLR4 and MyD88 and related inflammatory factors were found between the NC group and antagomiR-146a group. Compared with the NC group, agomiR-146a group showed markedly reduced ankle joint swelling index (p<0.05). Meanwhile, joint landing behavior and inflammatory swelling were significantly relieved in the agomiR-146a group (p<0.05). The mRNA and protein expression levels of TLR4 and MyD88 were remarkably decreased as well (p<0.05). Furthermore, the expression and distribution of NF-κB in synovial tissues of agomiR-146a group was markedly reduced when compared with the NC group (p<0.05). In addition, agomiR-146a group exhibited significantly lower expression levels of inflammatory factors (TNF-α, IL-1 and IL-6) in synovial tissues (p<0.05). MiR-146a alleviates joint inflammation of acute arthritis in rats through the TLR4/MyD88/NF-κB signaling pathway, which may become a new therapeutic target.