^(99)Tc-亚甲基二膦酸盐对胶原诱导性关节炎大鼠骨侵蚀的治疗作用

Effect of ^(99)technetium-methylenediphosphonate on bone erosion in collagen-induced arthritis rats

目的:观察99锝-亚甲基二膦酸盐(99technetium-methylenediphosphonate,99Tc-MDP)注射液对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠模型骨侵蚀的治疗作用,探讨其治疗骨侵蚀的有效作用成分及可能的作用机制。方法:建立CIA大鼠关节炎模型,分为模型组、帕米膦酸二钠组、MDP组和99Tc-MDP组,关节炎指数评价关节肿胀程度;放射学评分评价骨质破坏情况;HE染色观察关节病理组织形态学变化;ELISA检测血清中核因子κB受体活化因子配体(receptor activator of NF-κBligand,RANKL)、骨保护素(osteoprotegerin,OPG)和Dickkopf-1(DKK-1)的水平。结果:99Tc-MDP组、MDP组、帕米膦酸二钠组关节炎指数评分、骨质破坏评分均低于模型对照组(P<0.05);99Tc-MDP组与帕米膦酸二钠组、MDP组相比,差异有统计学意义(P<0.05);99Tc-MDP组、MDP组、帕米膦酸二钠组血清OPG水平高于模型组(P<0.05),血清RANKL和DKK-1水平低于模型组(P<0.05);99Tc-MDP组血清OPG水平高于帕米膦酸二钠组和MDP组(P<0.01),RANKL和DKK-1水平低于帕米膦酸二钠组和MDP组(P<0.01),但帕米膦酸二钠组和MDP组间差异无统计学意义(P>0.05)。结论:99Tc-MDP治疗CIA大鼠骨侵蚀的有效作用成分为99Tc与亚甲基二膦酸盐两者的螯合物,并且是通过促进OPG和抑制RANKL和DKK-1的表达发挥作用的。

Objective To examine the effects of 99 Tc-MDP on bone erosion in collagen-induced arthritis （CIA） rats, and to explore the effective component of 99 Tc-MDP and the underlying mechanism. Methods CIA rats were randomly divided into 4 groups： a CIA group, a pamidronate group, a MDP group and a 99 Tc-MDP group. Paw swelling, lesions of bone and cartilage, histopathologic changes of ankle joints and hind paws were assessed by arthritis index, radiographic analysis with Larsen score and HE staining, respectively. Serum levels of receptor activator of NF-κB ligand （RANKL）, osteoprotegerin （OPG） and Dickkopf-1 （DKK-1） were measured by enzyme linked immunosorbent assay.Results Compared with the CIA group, arthritis index and Larsen score of bone erosion in the 99 Tc-MDP group,the MDP group and the pamidronate group were significantly reduced （P0.05）. The reduction in bone erosion was more profound in the99 Tc-MDP than that in the MDP or the pamidronate group（P0.05）. Serum levels of OPG were significantly increased after treatment of 99 Tc-MDP or MDP or pamidronate （P0.05）. Whereas the serum levels of RANKL and DKK-1 were decreased after 99 Tc-MDP or MDP or pamidronate treatment （P0.05）. The effect of 99 Tc-MDP on RANKL, OPG or DKK-1 was more profound than that of MDP or pamidronate （P0.01）. Conclusion The chelate of 99 Tc-MDP is the active ingredient for treatment. The effect of 99 Tc-MDP on bone erosion is related to reducing the serum levels of RANKL and DKK-1 whereas increasing serum level of OPG.