Abstract: BACKGROUND: Traditional Chinese medicine methods for treating knee osteoarthritis include acupuncture and traditional Chinese medicine. Triptolide has anti-inflammatory and anti-cancer effects, and it also has significant effects in treating arthritis. However, its specific mechanism is still unclear.
OBJECTIVE: To investigate the effect of electroacupuncture combined with triptolide on the transforming growth factor-β signal pathway related to osteoarthritis. 
METHODS: Forty 8-week-old SPF mice were selected and fed for 1 week. Mice were then randomized into five groups: blank control group, model group, electroacupuncture group, triptolide group, and electroacupuncture combined with triptolide group (combined use group). A mouse model of knee osteoarthritis was established using intraarticular injection of monoiodoacetate in the latter four groups. After the model was successfully constructed, the mice in the blank control group and model group were raised normally; the mice in the electroacupuncture group were treated with electroacupuncture to stimulate the knee joints; the mice in the triptolide group were treated with intragastric administration of triptolide; and the mice in the combined use group were given electroacupuncture at the knee joints and intragastric administration of triptolide. Electroacupuncture was given once a day, and triptolide was administered once a day. Treatments in each group lasted for 4 weeks. Pressure-pain thresholds were observed in each group before and after treatment. Inflammation of the knee joint was evaluated by the macro scoring system. The peripheral blood samples of mice were collected to detect the levels of inflammatory factors, tumor transforming factor-α, interleukin-1β and interleukin-6, by ELISA kit. Western blot assay was used to detect the protein expression levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor β1 in mouse synovium and synovial fluid. 
RESULTS AND CONCLUSION: After intervention, compared with the model group, a great improvement in knee osteoarthritis was achieved in the electroacupuncture and triptolide groups (P < 0.05), and their combined use showed a better effect (P < 0.01). After intervention, the pain threshold of mice increased significantly in the electroacupuncture and triptolide groups compared with the model group (P < 0.05), and the pain threshold in the combined use group increased more significantly (P < 0.05). During the treatment, the arthritis score of mice in the model group gradually increased; compared with the model group, the arthritis scores decreased in the electroacupuncture and triptolide groups, and the score of the combined use group had a significant decline. After intervention, both electroacupuncture and triptolide significantly decreased the levels of tumor transforming factor-α, interleukin-1β and interleukin-6 in the peripheral blood of mice compared with the model group (P < 0.05), and their combined use could extremely significantly decrease the levels of these inflammatory factors in the peripheral blood of mice (P < 0.01). Western blot results revealed that after intervention, the expression levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor β1 were significantly increased in the synovium and synovial fluid of mice in the electroacupuncture group and the triptolide group compared with the model group (P < 0.05), while the expression levels of related proteins were extremely significantly increased (P < 0.01). It is suggested that electroacupuncture combined with triptolide may treat knee osteoarthritis in mice through transforming growth factor β signaling pathway.

Key words: electroacupuncture, triptolide, knee osteoarthritis, transforming growth factor β, inflammatory factor, mouse