局部应用唑来膦酸预防股骨头坏死塌陷  

Prevention of femoral head collapse due to osteonecrosis in rats by local delivery of zoledronate via polylactic-co-glycolic acid

作　　者：徐小龙[1] 苟文龙[2] 王程[1] 袁雪凌[1] 王玉[1] 彭江[1] 卢世璧[1] 郭全义[1] 汪爱媛[1] 许文静[1] 孟昊业[1] 刘舒云[1] 

机构地区：[1]解放军总医院骨科,北京市海淀区复兴路28号100853 [2]第三军医大学大坪医院骨科

出　　处：《中国矫形外科杂志》2015年第9期844-849,共6页Orthopedic Journal of China

基　　金：肢体重要组织损伤组织工程修复重建技术研发;国家863主题项目(编号:2012AA020502);肢体重要组织战创伤组织工程再生医学关键技术系列研究;全军十二五重点项目(编号:BWS11J025);严重创伤后骨;软骨;神经损伤修复与再生研究;国家973计划项目(编号:2012CB518106)

摘　　要：[目的]建立大鼠股骨头骨坏死动物模型,观察以聚乳酸-羟基乙酸共聚物(polylactic-co-glycolic acid,PLGA)为载体,局部应用唑来膦酸(zoledronate acid,ZOL)防止大鼠股骨头骨坏死塌陷的效果。[方法]选用PLGA作为局部应用ZOL的载体,制备含有30μg的ZOL的PLGA棒。取SD雄性大鼠30只,随机分为三组,建立创伤性股骨头骨坏死模型。股骨头钻孔,分别植入含有ZOL的PLGA棒(PLGA-ZOL组),以不含ZOL的PLGA棒(PLGA组)和空置(单纯打孔组)为对照组。6周后将大鼠处死取材,进行X线检查计量股骨头高度比,进行MicroCT扫描,分别计算比较各组的骨矿密度(bone mineral density,BMD)、骨体积分数(bone volume fraction,BVF)、骨小梁厚度(trabecular plate thickness,Tb.Th)和骨小梁间隙(trabecular spacing,Tb.Sp)。扫描后进行HE和Masson三色染色了解各组间组织学改变情况。[结果]与打孔组和PLGA组相比,PLGA-ZOL组中BMD(535.95±15.08,P<0.05),BVF(0.77±0.04,P<0.05)和Tb.Th(0.64±0.05,P<0.05)显著增加,而Tb.sp(0.37±0.06,P<0.05)显著降低,而打孔组和PLGA组并无统计学差异。而且PLGA-ZOL组股骨头有更好的形态,骨小梁保留更完整,新生骨更多。[结论]使用ZOL能够抑制局部骨吸收活动,促进局部骨生成,预防股骨头塌陷。[Objective] To determine the effectiveness of local delivery of 30 μg of zoledronate（ ZOL） in reducing femoral head deformation following ischemic osteonecrosis. [Methods] Poly（ lactic- co- glycolic acid）（ PLGA） cylinders were chosen as carriers for the ZOL,with the ZOL dose being 30 μg per cylinder. Osteonecrosis of the femoral head was induced in 30 Sprague Dawley rats by tying a ligature tightly around the femoral neck and transecting the round ligament,and the rats were randomly divided into no- PLGA,PLGA,and PLGA- ZOL groups. A tunnel was drilled into the top of the femoral head in all rats; it was left empty in the no- PLGA group,whereas a PLGA cylinder was inserted into it in the PLGA and PLGA- ZOL groups,containing no ZOL in the former and 30 μg ZOL in the latter. The rats were sacrificed 6 weeks after the operation,and radiography and micro- CT scans were used to evaluate the degree of deformation of the femoral heads and calculate the bone mineral density（ BMD）,bone volume fraction（ BVF）,trabecular thickness（ Tb. Th）,and trabecular spacing（ Tb. Sp）. Hematoxylin- eosin staining and Masson＇s trichrome staining were used to evaluate histological changes. [Results] BMD（ 535. 95± 15. 08,P〈0. 05）,BVF（ 0. 77 ± 0. 04,P〈0. 05）,and Tb. Th（ 0. 64 ± 0. 05,P〈0. 05） were significantly higher in the zoledronic acid group compared with the other groups, and Tb. Sp（ 0. 37 ± 0. 06, P〈0. 05） was significantly lower. However,no significant difference was found between the no- PLGA group and the PLGA group. Moreover,the PLGA-ZOL group showed better femoral head shape and more new bone formation. [Conclusion] Local use of ZOL can inhibit bone resorption and promote local bone formation,reducing deformation and preventing collapse of the femoral head after ischemic osteonecrosis.

关 键 词：股骨头骨坏死 成骨细胞 破骨细胞 唑来膦酸 

分 类 号：R681.8[医药卫生—骨科学]