重组核因子κB活化因子受体蛋白预防小鼠骨质疏松的研究  

Inhibitory effect of recombinant receptor activator of nuclear factor κB protein on bone loss in ovariectomized mice

作　　者：张里程[1] 吕厚辰[1] 熊琦[1] 张立海[1] 唐佩福[1] 

机构地区：[1]中国人民解放军总医院骨科,北京100853

出　　处：《中国骨伤》2013年第5期414-418,共5页China Journal of Orthopaedics and Traumatology

基　　金：国家自然科学基金(编号:81000796;30973068);军医进修学院博士研究生创新基金(编号:11BCZ02)~~

摘　　要：目的:探讨一种原核表达的重组核因子κB活化因子受体蛋白对破骨细胞活性及去卵巢小鼠骨质疏松预防作用,并与目前临床应用最广泛的抗骨质疏松药物-阿伦磷酸钠进行疗效对比。方法:雌性KM小鼠24只,3月龄,卵巢切除造模后按体重随机分3组:重组核因子κB活化因子受体蛋白组(1.5mg/kg,2次/周),阿伦磷酸钠治疗组(0.21mg/kg,1次/周),对照组(PBS缓冲液,0.2ml,2次/周)。给药12周后,通过体重、血清钙、血清磷、血清碱性磷酸酶、骨组织TRAP染色破骨细胞计数及Micro-CT检查进行疗效评估。结果:给药12周后,对照组骨密度(BMD)(92.600±14.319)mg/cc,骨小梁厚度(Tb.Th)(0.094±0.011)mm,骨小梁间距(Tb.Sp)(0.455±0.124)mm,骨体积分数(BVF)0.192±0.023,结构模型指数(SMI)1.388±0.328;重组核因子κB活化因子受体蛋白组BMD(133.050±13.022)mg/cc,Tb.Th(0.098±0.009)mm,Tb.Sp(0.365±0.105)mm,BVF(0.291±0.025)%,SMI 0.661±0.384;阿伦磷酸钠治疗组BMD(128.013±16.040)mg/cc,Tb.Th(0.097±0.011)mm,Tb.Sp(0.376±0.104)mm,BVF 0.281±0.024,SMI 0.753±0.307。重组核因子κB活化因子受体蛋白能有效抑制去卵巢引起的骨质疏松,具有与阿伦磷酸钠同等效果。与PBS对照组相比,重组核因子κB活化因子受体蛋白治疗组股骨远端BMD增加明显,BVF增加,骨小梁结构致密,Tb.Th明显变宽,Tb.Sp变窄,SMI降低,股骨远端脱钙切片TRAP染色破骨细胞几乎完全被抑制。结论:在小鼠骨质疏松模型中,重组核因子κB活化因子受体蛋白具有阿伦磷酸钠同等疗效,能明显抑制破骨细胞的吸收活性,并预防去卵巢引起的骨量丢失。Objective：To compare inhibitory effects of recombinant receptor activator of nuclear factor KB protein with bisphosphonate treatment （ALN） on osteoclasts activity and bone loss in ovarieetomized mice. Methods ：Twenty-four female KM mice were ovarieetomized bilaterally and treated with recombinant receptor activator of nuclear factor KB protein, alen- dronate, or PBS. Twelve weeks later,body weight, biochemical markers of bone metabolism, Micro CT scan and bone morphol- ogy were examined. Results ： After 12 weeks administration, the Micro CT scan and bone morphology values of each group were as follow. The control group：BMD （92.600±14.319） mg/cc,Tb.Th （0.094±0.011） mm,Tb.Sp （0.455±0.124） mm,BVF 0.192 ±0.023,SMI 1.388 ±0.328 ;the recombinant receptor activator of nuclear factor KB protein group ： BMD （ 133.050± 13.022） mg/cc,Tb.Th （0.098±0.009） mm,Tb.Sp （0.365±0.105） mm,BVF （0.291±0.025）%,SMI 0.661±0.384; the ALN group ：BMD （ 128.013 ±16.040） mg/cc ,Tb.Th （0.097±0.011） mm,Tb.Sp （0.376±0.104） mm,BVF 0.281 ±0.024, SMI 0.753 ± 0.307. In the ovariectomized mice experiments ,both recombinant receptor activator of nuclear factor κB protein and ALN sig- nificantly inhibited ovariectomy-induced bone loss. Compared to the control group （PBS） ,the recombinant receptor activator of nuclear factor KB protein group showed increased distal femur BMD and decreased trabecular spacing （Tb.Sp）,whereas the control group had significantly decreased distal femur BMD, significantly decreased Tb.Th, and increased Tb.Sp. There was a significant difference in bone volume fraction among the groups. The TRAP-positive osteoclasts in distal femur bone slices were nearly complete inhibited for Recombinant receptor activator of nuclear factor KB protein group and alendronate group. Conclusion： In vivo, recombinant receptor activator of nuclear factor KB protein effectively inhibits the activity of osteoclasts and the resulting bone loss ,which has a similar effect

关 键 词：骨质疏松 破骨细胞 卵巢切除术 小鼠 

分 类 号：R681[医药卫生—骨科学]