| Objective To explore the potential mechanism by which acupuncture knife therapy alleviates synovial inflammation in rheumatoid arthritis (RA) through the JAK2/STAT3/Bcl-2 signaling pathway. Methods Forty SD rats were randomly and equally divided into a control group, a CIA model group, a tofacitinib-treated group, and an acupuncture knife intervention group (n=10 per group). Except for the blank group, the other groups were induced with collagen to establish a CIA model, and tissue samples were collected after 28 days of intervention. Arthritis severity was determined by measuring ankle swelling and arthritis index scores. Ankle joint histopathology was examined via hematoxylin and eosin (HE) staining. Synovial concentrations of TNF-α, IL-6, and IL-1β were quantified with ELISA. RT qPCR was employed to quantify the transcriptional levels of p JAK2, p STAT3, Bcl 2, Bax, and caspase 3. Quantification of the p-JAK2/JAK2 and p-STAT3/STAT3 ratios was performed with Western blot analysis. A subsequent analysis via immunohistochemistry served to reveal the tissue localization and content of Bcl-2, Bax, and caspase-3 proteins. Results Relative to the control cohort, the CIA model animals demonstrated pronounced joint swelling and elevated arthritis index scores (P<0.01). Histological analysis revealed irregular cartilage surfaces along with hyperplastic and disorganized synovial cells. The synovial tissue in this group also showed substantially increased concentrations of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 (P<0.01). At the molecular level, there were significant upregulations in the p-JAK2/JAK2 and p-STAT3/STAT3 protein ratios and in Bcl-2 expression (both protein and mRNA), concurrent with a marked downregulation of Bax and caspase-3 expression (P<0.01). In contrast, both the acupuncture knife and tofacitinib interventions effectively ameliorated these pathological changes. These treatment groups presented significant reductions in joint swelling and arthritis index scores, accompanied by mitigated cartilage damage and a more organized, less cellular synovium (P<0.05, P<0.01). A significant decrease in the synovial levels of TNF-α, IL-1β, and IL-6 was also observed (P<0.05, P<0.01). Furthermore, these therapies led to a downregulation of the p-JAK2/JAK2 and p-STAT3/STAT3 ratios and Bcl-2 expression, while concurrently elevating the expression of the pro-apoptotic factors Bax and caspase-3 (P<0.05, P<0.01). Conclusion Needle-knife Tendon-sparing and Knot-dissolving Techniques may induce apoptosis of synovial cells and inhibit the release of pro-inflammatory factors such as TNF - α, IL-1 β, IL-6 by regulating the JAK2/STAT3/Bcl-2 signaling pathway, thereby alleviating RA synovitis. |