Regulatory Effects of Tetramethylpyrazine on Inflammation and Synoviocyte Proliferation and Apoptosis in Rats With Rheumatoid Arthritis

Abstract

**Objective:** To investigate the effects of tetramethylpyrazine (TMP) on inflammation, synoviocyte proliferation, and apoptosis in rats with rheumatoid arthritis (RA). **Methods:** One hundred male Sprague–Dawley rats were randomly assigned to five groups (n = 20): control, RA model, methotrexate (MTX, 10 mg/kg), low-dose TMP (30 mg/kg), and high-dose TMP (60 mg/kg). RA was induced by subcutaneous injection of Freund’s complete adjuvant into the right hind paw, except in the control group. From day 12 after induction, rats received the assigned treatments by intragastric administration for 14 days. Arthritis index (AI) was evaluated periodically. Synovial tissues were collected after sacrifice, and cultured synoviocytes were used to assess cell proliferation, apoptosis by flow cytometry, and Bcl-2/Bax protein expression by Western blotting. **Results:** Compared with the control group, AI scores increased significantly in the RA model group. MTX and both TMP treatments significantly reduced AI scores at days 18 and 26 (P < 0.05). Synoviocyte proliferation was markedly increased in the model group but was significantly inhibited by MTX and TMP. In contrast, synoviocyte apoptosis was reduced in the model group and significantly enhanced after MTX or TMP treatment. Furthermore, TMP decreased Bcl-2 expression and increased Bax expression compared with the model group (P < 0.05). **Conclusion:** TMP alleviates inflammation, suppresses abnormal synoviocyte proliferation, and promotes apoptosis in RA rats, possibly through regulation of the Bcl-2/Bax signaling pathway.