【摘要】 目的观察⁹⁹Tc-亚甲基二膦酸盐(⁹⁹Tc-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⁹⁹Tc-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、⁹⁹Tc-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、⁹⁹Tc-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⁹⁹Tc-MDP组（P＜0．05）；软骨破坏和骨质破坏评分,⁹⁹Tc-MDP组低于甲氨蝶呤组（P＜0．05）。③模型组、甲氨蝶呤组、⁹⁹Tc-MDP组MMP-3 mRNA水平显著高于正常组（P＜0．01）；模型组高于⁹⁹Tc-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⁹⁹Tc-MDP明显减轻CIA大鼠的关节炎症状,延缓关节破坏的进展；⁹⁹Tc-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。更多还原

【Abstract】 Objective To observe the treatment of ⁹⁹Te-MDP on typeⅡcollagen induced arthritis （CIA）in rat,and the effect on the expression of synovial MMP-3 and TIMP-1 mRNA.To explore the mech anisms of the ⁹⁹Te-MDP in the treatment of rheumatoid arthritis.Methods The rats in which C1A（n=24）were divided into three group:the control group（n=8）,⁹⁹Tc-MDP group（n=8）and Methotrexate group（n=8）. Arthritis were evaluated by arthritis index and histopathological index and the expressions of MMP-3 and TIMP-1 mRNA in synovium were detected by RT-PCR.Results①The arthritis indexs of the control group, the methotrexate group,the ⁹⁹Tc-MDP group were increased with time.②The histopathological scnres of the control group were significantly higher than those of methotrexate group and ⁹⁹Tc-MDP group（P＜0.01）.The histopathological scores of cartilage destruction and bone erosion of ⁹⁹Tc-MDP group were lower than those of methotrexate group（P＜0.05）.③The levels of MMP-3 mRNA of the control group,⁹⁹Tc-MDP group, methotrexate group were notably higher than those of the control group（P＜0.01）.The levels of control group was notably higher than that of the ⁹⁹Tc-MDP group（P＜0.05）.There was not significant difference in all groups on the levels of TIMP-1 mRNA（P＞0.05）.Conclusions ⁹⁹Tc-MDP can notably relieve the arthritis symdrome and retard the catilage damage and bone erosion of CIA in rats,and could significantly decrease the MMP-3 mRNA in the synovium.Which may be one of the therapeutic mechanism.⁹⁹Tc-MDP is better than methotrexate in retarding catilage and bone erosion and decreasing MMP-3 mRNA in CIA rats in a 3-week therapeutic intervention.更多还原