Therapeutic effect of methotrexate combined with electroacupuncture in rheumatoid arthritis rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Currently, methotrexate for rheumatoid arthritis has been explored; however, there are still some problems such as unsatisfactory treatment effects. OBJECTIVE: To investigate the therapeutic effect and mechanism of methotrexate combined with electroacupuncture in rheumatoid arthritis rats. METHODS: A total of 100 Wistar rats were selected, 80 of which were injected type II collagenase to induce rheumatoid arthritis models. After successful modeling, the model rats were randomly divided into model group, methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group. The remaining 20 normal animals untreated were used as the normal control group. The arthritis index was evaluated at 1, 6, and 12 weeks of treatment. Hematological changes in the ankle were observed with hematoxylin-eosin staining at 12 weeks after treatment. RT-PCR and western blot were used to detect changes in tumor necrosis factor α, JAK3, and STAT3 expression levels. Flow cytometry was used to detect the apoptotic rate of chondrocytes. RESULTS AND CONCLUSION: Compared with the model group, methotrexate and electroacupuncture alone or in combination could significantly reduce the arthritis index of rheumatoid arthritis rats at 1, 6, and 12 weeks after administration (P < 0.05), and the reduction tendency was more significant in the methotrexate+electroacupuncture group. There was no synovial tissue lesion and joint capsule hyperplasia in the normal control group. In the model group, synovial tissue was infiltrated by extensive inflammatory cells; vasodilation and vascular hyperplasia in the synovium triggered the formation of vascular pannus; and intrathecal ligament nerve injury and proliferation of synovial and fibrous tissues were observed. Histological changes in the synovium were less after treatment with methotrexate and electroacupuncture alone than in combination. Treatment with methotrexate plus electroacupuncture obviously decreased inflammatory cell infiltration and synovial hyperplasia. Compared with the model group, the levels of tumor necrosis factor-α, JAK3 and STAT3 mRNA and protein were significantly reduced in the methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group (P < 0.05), and the reduction was more significant in the methotrexate+electroacupuncture group (P < 0.05). The apoptotic rate of chondrocytes was highest in the model group, followed by the methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group (P < 0.05). However, the apoptotic rate of chondrocytes in the methotrexate+electroacupuncture group was still higher than that in the normal control group (P < 0.05). To conclude, the combination of methotrexate and electroacupuncture for rheumatoid arthritis can inhibit the activity of tumor necrosis factor and JAK-STAT pathways, reduce the apoptosis of chondrocytes, and protect the articular cartilage.