The effect of combined treatment of methotrexate and cyclophosphamide on synovial cell p53 expression incollagen-induced arthritis rats / 中华风湿病学杂志

ABSTRACT

Objective To investigate the effect of combination low-dose of methotrexate (MTX) and cy-clophosphamide (CTX) intermittent therapy on the synovial cell p53 expression of collagen-indued arthritis Rats. The possible synergistic effect is examined and the possible meehaniams are evaluated. Methods Models of CIA were successfully established in 75 female Wistar rats. The CIA rats were then randomized into controls. At the end of this 24-week study the synovium of ankle joints were obtained, fixed, decalcified, wrapped and cut into slices. The intensity of p53 mutations expressions was examined by immunohistochemi-stry method. Results The intensity of p53 mutations expression of synoviocytes in CIA model group was significantly higher than that in the controls. In addition, the p53 mutations expressions in the synoviocytes of the treatment groups were decreased markedly, which did not return to the baseline level. The improvement of p53 mutations in the combination treatment group was higher than the single treatment groups and the difference was statistically significant (P<0.05). However, the difference between the combination treatment group and high-dose MTX treatment group was not significant. Conclusion Low-dose of MTX combined with CTX has the same efficacy comparing to high-dose of MTX in inhibiting p53 expression of CIA rats synoviocytes, but it is superior to low-dose single drug group. The results suggest that the combination of MTX and CTX may be synergistic in the treatment of RA.