期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 79, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.106056
关键词
Naltrexone(NTX); Rheumatoid arthritis; Collagen-induced-arthritis(CIA) rat models; Opioid receptors; TLR4/NF- kappa B
资金
- Natural Science Foundation of Liaoning Province [20180550987]
- Natural Science Foundation of Shengyang [1801220]
Objective: Our aim was to study the efficacy and mechanism by which NTX alleviate arthritis in CIA rat models in vivo. Methods: Female Wistar rats were randomly divided into 6 groups, their weights were observed and the severity of arthritis and pathological changes were evaluated by HE staining. T lymphocyte subsets were detected by flow cytometry. The expression of cytokines was detected in peripheral serum by ELISA. Real time PCR, immunohistochemical staining and western blot analysis were utilized to detect the mRNA and protein expression of opioid receptors, TLR4, RANKL and /NF-kappa B in synovial tissue and the spleen. Results: The weight of the rats in the 10 mg/kg NTX group decreased the least, and had the least severe arthritis. CD4(+) T cells, Th1 cells and Treg cells increased, and CD8(+) T cells, Th1 cells and Th17 cells decreased in the splenic lymphocytes. The expression of proinflammatory cytokines decreased, and the expression of anti-inflammatory cytokines increased. MOR and DOR were strongly expressed in the spleen, whereas KOR and DOR were strongly expressed in synovial tissue. The expression of TLR4, NF-kappa B and RANKL was reduced in the spleen and synovium in the NTX group. Conclusions: NTX relieved the severity of arthritis in the CIA rat models at a concentration of 10 mg/kg by regulating T lymphocyte subsets and the expression of cytokines. NTX affected opioid receptors to inhibit the TLR4/NF-kappa B signaling pathway, regulating the systemic immune response and decreasing osteoclast differentiation, thereby alleviating inflammation and the erosion of articular cartilage along with bone tissue.
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