ATX抑制剂对OA小鼠骨保护的作用研究  

Effect of ATX inhibitors on bone protection in osteoarthritic mice

作　　者：史佳妮 戴天琪 王艳丽[1] 张志毅[1] SHI Jia⁃ni;DAI Tian⁃qi;WANG Yan⁃li;ZHANG Zhi⁃yi(Department of Rheumatology and Immunology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院风湿免疫科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2024年第5期457-461,共5页Journal of Harbin Medical University

基　　金：国家自然科学基金青年科学基金项目(82001716);黑龙江省卫生健康委课题(2020-103);哈尔滨医科大学附属第一医院科研创新基金(20201318);哈尔滨医科大学附属第一医院优秀青年项目(2024YQ13)

摘　　要：目的 探讨自分泌运动因子(autotaxin, ATX)抑制剂HA130对骨关节炎(osteoarthritis, OA)小鼠骨的保护作用。方法 将15只C57BL6小鼠随机分为假手术组、手术组、药物注射组,每组各5只,手术组和药物注射组分别通过膝关节内侧半月板失稳术(destabilization of the medial meniscus, DMM)构建模型。药物注射组术后第2、4、6和8周将HA130注射到小鼠膝关节腔内,手术组小鼠进行关节腔内等体积溶剂注射,假手术组小鼠不做处理,3组小鼠于术后10周通过微计算机断层扫描技术(micro computed tomography, Micro-CT)进行观察和评估。结果 影像学显示,ATX抑制剂HA130减轻了骨破坏程度、增加了骨小梁数目;骨相关参数中骨体积分数(bone volume/total volume, BV/TV)、骨表面积组织体积比值(bone surface/tissue volume, BS/TV)、骨小梁厚度(trabecular thickness, Tb.Th)、骨小梁数量(trabecular number, Tb.N)、骨小梁连接密度(connectivity density, Conn.D)、皮质面积分数(cortical bone area/total area, Ct.Ar/Tt.Ar)及皮质内周长(endocortical perimeter, Ec.Pm)增高(P<0.05);骨矿物质密度(bone mineral density, BMD)、椭圆体截距长度平均值(mean intercept length, MIL)降低(P<0.05)。结论 影像学和骨参数分析均证明了ATX抑制剂对OA小鼠骨具有保护作用。Objective To investigate the protective effect of autotaxin(ATX)inhibitor HA130 on osteoarthritis(OA)in mice.Methods Fifteen C57BL6 mice were randomly divided into the sham⁃operation group,the operation group and the drug injection group,with 5 mice in each group.The operation group and the drug injection group were constructed as models by destabilization of the medial meniscus(DMM)of the knee joint.HA130 was injected into the knee joint cavity of the mice in the drug injection group at weeks 2,4,6,and 8 postoperative⁃ly,the mice in the operation group underwent intra⁃articular isovolumic solvent injections,and the mice in the sham⁃operation group were left untreated,and the mice in the three groups were observed and evaluated by micro computed tomography(Micro⁃CT)at 10 weeks postoperative⁃ly.Results Imaging showed that the ATX inhibitor HA130 was attenuated the degree of bone destruction and increased the number of trabecular bone;among the bone⁃related parameters,bone volume/total volume(BV/TV),bone surface/tissue volume(BS/TV),trabecular thick⁃ness(Tb.Th),trabecular number(Tb.N),connectivity density(Conn.D),cortical bone are⁃a/total area(Ct.Ar/Tt.Ar)and endocortical perimeter(Ec.Pm)were increased(P<0.05)and bone mineral density(BMD),mean intercept length(MIL)were decreased(P<0.05).Conclusion Both imaging and bone parameter analysis demonstrate the protective effect of ATX inhibitors on OA in mice.

关 键 词：骨关节炎 自分泌运动因子 ATX抑制剂 微计算机断层扫描技术 

分 类 号：R684.3[医药卫生—骨科学]