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目的观察~(99)Tc-亚甲基二膦酸盐(~(99)Tc-MDP)对Ⅱ型胶原诱导性关节炎(CIA)大鼠的治疗作用及其对滑膜基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制物-1(TIMP-1)的影响,探讨~(99)Tc-MDP治疗类风湿关节炎(RA)的机制。方法建立CIA大鼠关节炎模型,分为正常对照组、模型对照组、~(99)Tc-MDP组和甲氨蝶呤组。采用关节炎指数评分法评价其关节的炎症程度；观察关节病理组织形态学变化；反转录-聚合酶链反应(RT-PCR)法检测滑膜MMP-3和TIMP-1 mRNA水平。结果①模型组、甲氨蝶呤组、~(99)Tc-MDP组大鼠随着免疫时间延长关节炎指数(Al)评分增加。②模型组关节组织学评分均高于甲氨蝶呤组和~(99)Tc-MDP组(P＜0．05)；软骨破坏和骨质破坏评分,~(99)Tc-MDP组低于甲氨蝶呤组(P＜0．05)。③模型组、甲氨蝶呤组、~(99)Tc-MDP组MMP-3 mRNA水平显著高于正常组(P＜0．01)；模型组高于~(99)Tc-MDP组(P＜0．05)。各组滑膜TIMP-1 mRNA水平差异无统计学意义(P＞0．05)。结论~(99)Tc-MDP明显减轻CIA大鼠的关节炎症状,延缓关节破坏的进展；~(99)Tc-MDP降低滑膜MMP-3 mRNA水平,可能是其治疗RA的机制之一；在延缓CIA大鼠软骨和骨质破坏的病理学改变及降低滑膜MMP-3 mRNA水平,其近期疗效优于甲氨蝶呤。
Objective To observe the therapeutic effect of ~ (99) Tc-methylene diphosphonate (~ (99) Tc-MDP) on type Ⅱ collagen induced arthritis (CIA) rats and its effect on synovial matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the treatment of rheumatoid arthritis (RA). Methods The arthritis models of CIA rats were established and divided into normal control group, model control group, ~ (99) Tc-MDP group and methotrexate group. The arthritis index score was used to evaluate the degree of inflammation in the joints. Morphological changes of joint pathology were observed. The levels of MMP-3 and TIMP-1 mRNA in synovium were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results ① The AI of model group, methotrexate group and ~ (99) Tc-MDP group increased with the prolongation of immunization time. (2) The joint histological scores of model group were higher than those of methotrexate group and 99Tc-MDP group (P <0.05). The scores of cartilage destruction and bone destruction were lower in 99Tc-MDP group Methotrexate group (P <0.05). The levels of MMP-3 mRNA in model group, methotrexate group and ~ (99) Tc-MDP group were significantly higher than those in normal group (P <0.01), and higher in model group than in 99 Tc-MDP group <0.05). There was no significant difference in TIMP-1 mRNA expression in each group (P> 0.05). Conclusions ~ (99) Tc-MDP can significantly reduce the arthritis symptoms and delay the progression of joint destruction in CIA rats. 99 99 Tc-MDP can decrease the MMP-3 mRNA level in synovium, which may be one of the mechanisms of its treatment. It is better than methotrexate in delaying the pathological changes of cartilage and bone destruction and decreasing the MMP-3 mRNA level in synovium of CIA rats.