中国医院用药评价与分析2024，Vol.24Issue(9)：1075-1079,1084,6.DOI:10.14009/j.issn.1672-2124.2024.09.012
硼替佐米与帕米膦酸二钠在大鼠肢体废用性骨质疏松症模型中的疗效比较
Comparison on the Efficacy of Bortezomib and Pamilophosphate in the Rat Model of Disuse Osteoporosis
摘要
Abstract
OBJECTIVE:To compare the efficacy of bortezomib and pamilophosphate in the rat model of disuse osteoporosis(DOP).METHODS:Forty 16-week-old male SD rats were randomly divided into the control group,sham surgery group,model group,pamilphosphate treatment group and bortezomib treatment group,with 8 rats in each group.DOP rat model was established.The microstructural parameters of hind limb tibia were determined by micro-CT.Serological indexes receptor activator of nuclear factor-κB ligand(RANKL)/osteoprotegerin(OPG)concentration ratio,serum Sclerostin and alkaline phosphatase(ALP)levels were determined by enzyme linked immunosorbent assay.The mRNA expression levels of bone resorption-related factors type I procollagen amino-terminal prepeptide(PINP),C-terminal crosslinking telopeptide of type I collagen(CTX)-1,matrix metalloproteinase(MMP)-3 were determined by quantitative polymerase chain reaction.Signaling axis of Calcineurin/nuclear factor of activated T-cells isoform(NFAT)and signaling pathway of glycogen synthase kinase-3β(GSK3β)/protein kinase B(Akt),a key transcription factor for osteogenic differentiation,were determined by Western blotting.RESULTS:Compared with sham surgery group,bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),connectivity density(Conn.D),structural model index(SMI),bone mineral density(BMD)and trabecular separation(Tb.Sp)of the posterior limb tibia in model group rats decreased,trabecular separation(Tb.Sp)increased;serum RANKL/OPG concentration ratio and serum sclerostin level increased,serum ALP level decreased;the relative expression levels of PINP and CTX-1 mRNA in bone tissues decreased,while the relative expression levels of MMP-3 and MMP-9 mRNA increased,the relative expression levels of Calcineurin decreased;the relative expression levels of p-Akt decreased,and the relative expression levels of p-GSK3 increased,with statistically significant differences(P<0.05).Compared with the model group,the pamilphosphate treatment group and bortezomib treatment group partially reversed the above indicators(including BV/TV,Tb.N,Tb.Th,Tb.Sp,Conn.D,SMI and BMD in posterior limb tibia,serum RANKL/OPG concentration ratio,levels of Sclerostin and ALP,the relative expression levels of MMP-3 and MMP-9 mRNA in bone tissues,the relative expression levels of Calcineurin in bone tissues,and the relative expression levels of p-Akt and p-GSK3β in bone tissues),with statistically significant differences(P<0.05).The relative expression levels of PINP and CTX-1 mRNA and the relative expression levels of NFAT in bone tissues of rats in bortezomib treatment group increased,with statistically significant difference(P<0.05).Compared with the pamilophosphate treatment group,bortezomib treatment group had a more significant effect on reversing the above indicators,the differences were statistically significant(P<0.05).CONCLUSIONS:The efficacy of bortezomib for DOP rat model is better than that of pamilophosphate.关键词
废用性骨质疏松症/二磷酸盐/硼替佐米/Calcineurin/NFAT信号轴/GSK3β/Akt信号通路Key words
Disuse osteoporosis/Biphosphate/Bortezomib/Calcineurin/NFAT signaling axis/GSK3β/Akt signaling pathway分类
医药卫生引用本文复制引用
程千纲,王博,叶永奇,吴涛,梁智锋,贾永兴,杨英才..硼替佐米与帕米膦酸二钠在大鼠肢体废用性骨质疏松症模型中的疗效比较[J].中国医院用药评价与分析,2024,24(9):1075-1079,1084,6.基金项目
山西省卫生健康委科研课题(No.2023071) （No.2023071）
