Abstract: Objective To investigate the effects of tetramethylpyrazine (TMP) on the extracellular regulated protein kinase (ERK) pathway in collagen-induced arthritis rats. Methods Thirty male SD rats were randomly divided into control group, model group and TMP group, with 10 rats in each group. The rats in the model group and the TMP group were modeled with collagen-induced arthritis. After the successful modeling, the TMP group was treated daily with TMP (0.1 g/kg) by intragastric administration, for continuous 28 d. The model group and the normal group were given the same volume of physiological saline. The volume changes of the hind paws in the three groups were measured weekly, and the inflammatory cell infiltration of each group was observed by HE staining. The levels of tumor necrosis factor α (TNF-α), angiopoietin 1 (Ang-1), interleukin 1β (IL-1β) and vascular endothelial growth factor (VEGF) in synovial tissue and serum of rats were detected by realtime PCR and ELISA, respectively. The expressions of ERK pathway-related proteins in synovial tissues were detected by Western blotting. Results From the second week after modeling, the hind paw volume in the model group was higher than that in the control group (P<0.05), and the one in the TMP group was lower than that in the model group (P<0.05). The expression levels of inflammatory factors TNF-α, Ang-1 and IL-1β in the model group and the TMP group were higher than those in the control group (P<0.05), but the ones in the TMP group were lower than those in the model group (P<0.05). The level of VEGF in the synovial tissue of rats in the TMP group was lower than that of the model group (P<0.05). The expression of p-ERK1/2 protein in the model group and the TMP group was increased (P<0.05), and the expression level of p-ERK1/2 protein in the TMP group was lower than that of the model group (P<0.05). Conclusion TMP can effectively regulate the levels of TNF-α and IL-1β in serum and synovial tissue of rats with collagen-induced arthritis and alleviate the symptoms of joint swelling by inhibiting the ERK pathway.

Key words: Tetramethylpyrazine, Collagen-induced arthritis, Extracellular regulated protein kinase pathway, Inflammatory factor, Rats