[Effect of moxibustion on the cGAS/STING signaling pathway in synovial tissue of rats with rheumatoid arthritis].

Abstract

Objectives: To investigate the effect of moxibustion on the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway in the synovial tissue of knee joints in rheumatoid arthritis (RA) model rats, and to explore the mechanism by which moxibustion alleviates synovial inflammatory injury.

Methods: Forty male SD rats were randomly divided into 4 groups (10 rats in each group):blank, model, moxibustion, and triptolide groups. The RA model was induced by injecting complete Freund's adjuvant into the right hind toe combined with exposure to wind, cold, and damp environments. The moxibustion group received daily 20 min treatment at "Zusanli" (ST36) or "Shenshu" (BL23) for 15 d;the triptolide group was administered triptolide suspension (8 mg/kg) via gavage for 15 d. The joint swelling degree of right hind toe was measured by water displacement;the synovial morphology was assessed via HE staining;the mitochondrial ultrastructure was observed by transmission electron microscopy;the synovial protein expression levels of cGAS, STING, TANK-binding kinase 1 (TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3) and phosphorylated nuclear factor-kappa B p65(p-NF-κB p65) were detected by Western blot;serum contents of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), C-X-C motif chemokine ligand 10 (CXCL10), and interferon-β (IFN-β) were measured by ELISA.

Results: Compared with the blank group, the model group showed increased joint swelling degree (P<0.01), irregular synovial lining cell distribution, marked hyperplasia, and inflammatory cell infiltration;synovial cGAS, STING, TBK1, p-IRF3, and p-NF-κB p65 protein expression levels and serum IL-6, ICAM-1, CXCL10, and IFN-β contents were significantly elevated (P<0.01). Compared with the model group, both moxibustion and triptolide interventions reduced joint swelling degree (P<0.01), improved synovial histopathology, and down regulated the aforementioned proteins and cytokines (P<0.01). No significant differences were observed between the moxibustion and triptolide groups.

Conclusions: Moxibustion attenuates joint swelling, inflammatory cytokine release, and synovial injury in RA model rats, potentially via suppression of the cGAS/STING pathway.