To investigate the possible mechanism of action of sinomenine (Sin) in the treatment of collagen-induced arthritis (CIA) rats by regulating macrophage polarization.

Wistar rats were randomly divided into control group (normal diet and care), model group (CIA model was established with bovine type Ⅱ collagen at the tail), experimental-L, -M, -H groups (all on the basis of the model group, 40, 80 and 160 mg·kg^-1 Sin by gavage respectively), inh-NC group and inh-miR-885-5p group[on the basis of the experimental-H group, the two groups were injected with a negative control of microRNA-885-5p (miR-885-5p) and miR-885-5p inhibitor in the tail vein, respectively)], for four weeks, with 10 rats in each group. The arthritis index (AI) and plantar swelling of rats in each group were statistically analyzed. The pathological conditions of the synovial tissue of the ankle joint were observed by hematoxylin-eosin staining. Real-time fluorescent quantitative polymerase chain reaction was performed to examine the relative expression level of miR-885-5p in rat synovial tissue. Western blot was carried out to detect the expression of related proteins in the synovial tissue of rats. Enzyme-linked immunosorbent assay was used to detect the level of serum inflammatory factors. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) was used to detect the apoptosis of rat synovial cells.

The AI scores of the control group, model group and experimental-H group were 0, (7.20±1.38) and (5.50±1.10) scores, respectively; the paw swelling were 35.32±7.05, 72.46±14.47 and 51.65±10.31, respectively; the relative expression levels of miR-885-5p were 1.00±0.18, 0.52±0.10 and 0.71±0.14, respectively. The relative expression levels of suppressor of cytokine signaling 1 (SOCS1) protein in the control, model group, experimental-H group, inh-NC group and inh-miR-885-5p group were 1.00±0.18, 0.51±0.10, 0.75±0.15, 0.71±0.14 and 0.55±0.11, respectively; the levels of interleukin (IL)-6 were (35.29±7.05), (215.82±43.15), (121.33±24.25), (115.62±23.08) and (207.39±41.36) pg·mL^-1, respectively; the apoptosis rates were (31.47±6.29)%, (12.19±2.43)%, (22.03±4.41)%, (20.16±4.03)% and (13.37±2.66)%, respectively. The above indexes in the experimental-L, -M, -H groups were dose-dependent, and the differences in the above indexes between the experimental-H group and the control group were statistically significant compared with the model group (P<0.05, P<0.01, P<0.001), and the differences in the above indexes between the inh-miR-885-5p group and the inh-NC group were also all statistically significant (all P<0.05).

Sin can regulate macrophage polarization, and improve synovial inflammation in CIA rats, which may be related to the up-regulation of miR-885-5p expression and activation of SOCS1/signal transducer and activator of transcription 3 (STAT3) signaling pathway.