Methotrexate plus electroacupuncture reduces autophagy in ankle synovial tissue in rats with rheumatoid arthritis

Am J Transl Res. 2023 Apr 15;15(4):2747-2756. eCollection 2023.

Abstract

Objective: To explore the effect of methotrexate combined with electroacupuncture on autophagy in the ankle synovial tissue in rats modeled with rheumatoid arthritis.

Methods: A rat model of rheumatoid arthritis was constructed by Freund's complete adjuvant injection. The animals were then randomly grouped into the methotrexate + electroacupuncture, methotrexate, electroacupuncture, and model groups. The left hindfoot plantar volume, histopathological morphology of the ankle joint synovium, and autophagy-related genes were detected and compared after the intervention.

Results: In comparison with the model group, significantly reduced plantar volume and mRNA and protein levels of autophagy-related gene (Atg) 3, Atg5, Atg12, unc-51-like kinase 1 (ULK1), Beclin1, and light chain 3 (LC3), as well as alleviated synovial hyperplasia were identified in the methotrexate and electroacupuncture groups. The improvement in the above indicators was more pronounced in the methotrexate + electroacupuncture group.

Conclusions: By inhibiting autophagosome formation, both methotrexate and electroacupuncture inhibit synovial cell autophagy, alleviate synovial cell hyperautophagy, and relieve abnormal synovial hyperplasia, thus exerting a protective effect on the joint synovium. The combination of treatment with methotrexate and electroacupuncture works best.

Keywords: Methotrexate; ankle synovial tissue; autophagy; electroacupuncture; rheumatoid arthritis rats.