99Tc-亚甲基二膦酸盐对胶原诱导性关节炎大鼠滑膜及软骨凋亡相关因子的影响

Objective Collagen induced arthritis (CIA) rats is an animal model of human rheuma-toid arthritis (RA). It is widely used in research of the pathogenesis and the therapeutic targets of RA. This paper was to investigate the therapeutic action of 99Tc-methylene diphosphonic acid (MDP) on CIA rats and its effects on the expression of apoptosis associated factor bcl-2 and bax in synoviocytes and articular chon-drocytes. Methods CIA rat models were carried out by subcutaneous injection with bovine collagen Ⅱ and incomplete Freud's adjuvant. Rats were divided into four groups: control group, CIA model group (the CIA rats were infused with physiological saline via tail vein daily), 99Tc-MDP group (the C1A rats were injected with 99Tc-Mi)P 0.04 μg 99Tc/kg via tail vein daily) and methotrexate (MTX) group (the CIA rats were in-jected with MTX 1 mg/kg via tail vein weekly). The signs of arthritis were evaluated by arthritis index (AI) scores. Immunohistochemistry was performed to detect the expression of bcl-2 and bax in synoviocytes and articular chondrocytes. SPSS 13.0 was used for data analysis. Results (1) The signs of arthritis, AI scores and pathological changes of arthrosynovitis in CIA rats were significantly improved by 99Tc-MDP orMTX. (2) The expression of bcl-2 and box in the synoviocytes of CIA model group [(39.30 ± 0.53) %, (27.37 ±2.45)%] was significantly increased compared with control group [(7.56 ± 1. 18)% , (6.14 ± 1.71) % ; q = 46.27, 24.57, all P < 0.001]. In the synovioeytes of 99Tc-M DP group and MTX group, the level of bcl-2 was remarkably decreased [(30.24 ± 2.09) %, (27.25 ± 3.33) %] compared with CIA model group (q = 13.20, 17.56, all P <0.001), while the level of bax was slightly increased and the ratio of bcl-2/bax was significantly decreased. (3)The expression level of bcl-2 and bax in the articular chondro-cytes of CIA model group [(20.20 ± 2.78) %, (36.40 ± 1.67) %] was significantly higher than control group [(9.91±4.09)%, (6.71 ±3.50)%; q=10.51, 37.01, allP<0.001]. Compared with CIA model group, the expression level of bcl-2 in articular chondrocytes of 99Tc-MDP group [(26. 58 ± 2. 52) %] and MTX group [(27.06 ± 1.92) %] was remarksbly increased [(24.26 ± 2.75) %, (23.53 ± 0.74) % ; q = 6.53, 7.01, all P < 0.001]. And the expression level of bax was significantly decread (q = 15.12, 16.04, all P <0. 001) and the ratio of bcl-2/bax was significantly increased. Conclusions The ab-normal expression of apoptosis associated factor bcl-2 and bax in synoviocytes and articular chondrocytes was closely related to the occurrence and progression of signs in CIA rats. 99Tc-MDP could improve the signs of arthritis, meanwhile regulate the expression of bcl-2 and bax in synoviocytes and articular ehondrocytes, suggesting that one of the therapeutic mechanisms of 99Tc-MDP might be related to stimulated synoviocytes apoptosis and reduced articular chondrocytes apoptosis.

Effects of 99Tc-MDP on synoviocytes and articular chondrocytes apoptosis associated factors on CIA rats