唑来膦酸与伊班膦酸对破骨细胞抑制作用比较  

Comparison of inhibitory effects of zoledronic acid and ibandronate on osteoclasts

作　　者：李鹏飞 贾楠[2] 王金星[2] 梁军伟[2] 赵学良 杜乃熠 李凤菊 赵宗茂 Li Pengfei;Jia Nan;Wang Jinxing;Liang Junwei;Zhao Xueliang;Du Naiyi;Li Fengju;Zhao Zongmao(Department of Neurosurgery,the Second Hospital of Hebei Medical Univercity,Shijiazhuang 050061,China;Department of Spine,Harrison International Peace Hospital,Hengshui 053000,China;Department of Radiology,Hebei Provincial Corps Hospital of Chinese People′s Armed Police Forces,Shijiazhuang 050050,China)

机构地区：[1]河北医科大学第二医院神经外科,石家庄050061 [2]哈励逊国际和平医院脊柱科,衡水053000 [3]武警河北总队医院放射科,石家庄050050

出　　处：《中华实验外科杂志》2021年第7期1210-1213,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(81870984);河北省自然科学基金(H2015206309);河北省国际科技合作基地建设专项(193977143D);2017年河北省政府资助临床医学优秀人才培养和基础课题研究项目;2019年河北省政府资助临床医学优秀人才培养项目;河北省人才工程培养资助项目(A201901115)。

摘　　要：目的:探讨唑来膦酸和伊班膦酸抑制破骨细胞分化及骨吸收功能特征。方法:诱导C57小鼠骨髓单核细胞向破骨细胞分化。依据双膦酸盐种类不同分为3组,对照组采用α-MEM培养基常规孵育,加入磷酸盐缓冲液;唑来膦酸组培养基中分别加入浓度为1×10-8、1×10-7、1×10-6、1×10-5、1×10-4mol/L唑来膦酸;伊班膦酸组加入相同梯度浓度伊班膦酸。通过抗酒石酸酸性磷酸酶染色比较细胞形成及黏附性;应用Transwell系统检测细胞迁移性;采用骨基质培养检验细胞骨吸收性,并定量分析。组间比较采用单因素方差分析。结果:与对照组染色阳性多核细胞数[(118.5±12.7)个]比较,1×10-6mol/L唑来膦酸破骨细胞形成数量明显减少至(26.6±5.2)个,为其阈浓度;抑制效果优于同浓度伊班膦酸[(99.2±10.9)个,F=5.531,P<0.05]。而伊班膦酸到达1×10-5mol/L阈浓度才发挥有效抑制作用[(27.3±6.1)个]。与对照组附壁生长及跨膜细胞数[(131.7±15.3)、(111.6±13.5)个]比较,1×10-6mol/L唑来膦酸[(72.8±12.8)、(35.8±6.8)个]比同浓度伊班膦酸[(128.6±13.6)、(98.6±9.6)个]更显著抑制破骨细胞黏附与迁移性(F=2.638、3.976,P<0.05)。与对照组骨吸收陷窝数[(28.1±7.2)个]比较,1×10-6mol/L唑来膦酸[(5.8±2.6)个]比同浓度伊班膦酸[(26.9±6.6)个]抑制细胞骨吸收性更显著(F=3.215,P<0.05)。结论:1×10-6mol/L唑来膦酸即发挥有效抑制破骨细胞作用,而伊班膦酸阈浓度为1×10-5mol/L。Objective To investigate the characteristic inhibitory effects of zoledronic acid and ibandronate on the differentiation and bone resorption of osteoclasts.Methods Bone marrow mononuclear cells of C57 mice were induced and differentiated to osteoclasts.According to the types of bisphosphonates,three groups were divided.Phosphate buffer was used as control group andα-MEM medium was used for routine incubation.In zoledronic acid group,1×10-8,1×10-7,1×10-6,1×10-5,1×10-4mol/L zoledronic acid was added to medium.In ibandronate group,the same gradient concentration of ibandronate was added to medium.Tartrate resistant acid phosphatase staining was used to observe and compare differentiation and adhesion effects of osteoclasts.Bone resorption of osteoclasts was measured by bone matrix culture and quantitative analysis.One way ANOVA was used to compare the results between two groups.Results Compared to positive multinucleated cells in control group(118.5±12.7),zoledronic acid had an effective inhibitory effect(26.6±5.2)at 1×10-6 mol/L;however,1×10-6 mol/L ibandronate exerted a more effective inhibitory effect(99.2±10.9).Ibandronate could effectively suppress osteoclasts(27.3±6.1)when the threshold concentration reached 1×10-5 mol/L(F=5.531,P<0.05).compared to adhesion and migration ability in control group(131.7±15.3,111.6±13.5),1×10-6 mol/L zoledronic acid(72.8±12.8,35.8±6.8)significantly inhibited adherent growth and transmembrane osteoclasts,more significant than ibandronate(128.6±13.6,98.6±9.6)at 1×10-6 mol/L(F=2.638,3.976,P<0.05).compared to bone resorption of control group[(28.1±7.2)cells],1×10-6 mol/L zoledronic acid[(5.8±2.6)cells]showed significant inhibitory effect,more significant than 1×10-6 mol/L ibandronate[(26.9±6.6)cells,F=3.215,P<0.05].Conclusion Zoledronic acid can effectively suppress osteoclasts at 1×10-6 mol/L.However,threshold concentration of ibandronate is 1×10-5mol/L.

关 键 词：破骨细胞 分化 唑来膦酸 伊班膦酸 

分 类 号：R965[医药卫生—药理学]