摘要
目的探讨巨噬细胞炎症蛋白⁃1α(MIP⁃1α)拮抗剂联合硼替佐米通过抑制Erk1/2/Bax促进骨髓瘤骨病(myeloma bone disease,MBD)成骨作用。方法采用皮下注射骨髓瘤细胞株方法构建MBD小鼠模型,按药物给予分为对照组、硼替佐米(Bor)组、Bx471(MIP⁃1α拮抗剂)组、硼替佐米(Bor)联合Bx471(MIP⁃1α拮抗剂)组;ELISA检测MIP⁃1α、SOST、IL⁃6、BALP、RANKL、OPG水平,Western blot检测Erk、Bax、Caspase 3、Caspase 9表达水平,X线评估骨质破坏程度。结果X线显示荷瘤小鼠(对照组)出现病理性骨折,Bor组、Bx471组及Bor联合Bx471组骨质破坏程度低于对照组。对照组的MIP⁃1α、SOST、RANKL、IL⁃6水平高于Bor组及Bx471组(P<0.05),明显高于Bor联合Bx471组(P<0.001),而OPG、BALP的表达明显低于Bor联合Bx471组(P<0.001)。对照组的Erkl/2、Bax、Caspase 3、Caspase 9蛋白表达高于Bor组及Bx471组(P<0.05),且明显高于Bor联合Bx471组(P<0.001)。结论MIP⁃1ɑ拮抗剂联合硼替佐米可能抑制Erk1/2/Bax信号通路促进MBD成骨作用。
Objective To investigate the role of MIP-1α antagonist combined with bortezomib in the facilitation of osteoblasts in myeloma bone disease(MBD)by inhibiting Erk1/2/Bax.Methods A MBD mouse model was constructed by subcutaneous injection of myeloma cell lines.The mice were divided into four groups:the control group,Bortezomib(Bor)group,MIP-1α antagonist(Bx471)group,Bor combined with Bx471(Bor+Bx471)group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of MIP-1α,SOST,IL-6,BALP,RANKL,and OPG and Western blotting the expression levels of Erk,Bax,Caspase 3,Caspase 9,and X-ray to assess the degree of bone destruction.ResultsX-ray tests showed that the tumor-bearing mice in the control group had pathological fractures.As compared with the control group,the bone destructions in the other three groups were at a lower level.In contrast,the levels of MIP-1α,SOST,RANKL,and IL-6 in the control group were significantly higher than in Bor group and Bx471 group(P<0.05),especially than in Bor+Bx471 group(P<0.001),while the expressions of OPG and BALP were significantly lower than in the Bor combined with Bx471 group(P<0.001).The protein expressions of Erkl/2,Bax,Caspase 3,Caspase 9 in the control group were higher than in Bor group and Bx471 group(P<0.05),especially than in Bor+Bx471 group(P<0.001).Conclusion sMIP-1αantagonists combined with bortezomib may inhibit the Erk1/2/Bax signaling pathway and then promote MBD osteoblasts.
作者
陈卫琼
蒋芳
王姗姗
黄勃
屈付君
黄林
王晓桃
CHEN Weiqiong;JIANG Fang;WANG Shanshan;HUANG Bo;QU Fujun;HUANG Lin;WANG Xiaotao(The Second Affiliated Hospital of Guilin Medical College,Guilin 541100,China)
出处
《实用医学杂志》
CAS
北大核心
2021年第12期1529-1533,共5页
The Journal of Practical Medicine
基金
国家自然科学基金(编号:82060044)
广西自然科学基金(编号:2020aXNSFAA159018)。
