首页> 中文期刊> 《陕西医学杂志 》 >核心结合因子α1基因修饰MSCs对骨质疏松大鼠骨形成作用研究

核心结合因子α1基因修饰MSCs对骨质疏松大鼠骨形成作用研究

             

摘要

目的:以去势大鼠建立绝经后骨质疏松模型,探讨以核心结合因子α1(Cbfα1)基因修饰骨髓间充质干细胞(MSCs)作为种子细胞,对绝经后骨质疏松症骨形成的刺激作用和基因治疗机制.方法:54只SD雌性大鼠随机分为三组:去势后给药实验组(Cbfα1基因修饰MSCs植入组:(G1),去势组(G2)和对照组(G3),并将术后第4、10和16定为实验周.观测骨形成指标:骨钙素(BGP)、骨特异性碱性磷酸酶(骨AKP)和总碱性磷酸酶(总AKP)和骨吸收指标:尿吡啶醚(PYD)和脱氧吡啶醚(DPD)以及骨生物力学检测(BMT).同步用IBAS计算机全自动图像分析系统对不脱钙骨组织动态观测骨形态计量学参数.结果:G1在去势后4~16周BGP和骨AKP明显高于G2.而骨吸收指标:尿PYD和DPD两组间无显著差异.骨形成表面(FS)和骨小梁体积比(TBV),骨小梁平均厚度(MTT)较G2明显升高,尤其是TBV和FS,这种差异在第10周最为显著.随着给药时间的延长(第16周)骨矿化沉积速率(MAR)逐渐增加.骨吸收表面(RS)与G2比较在所有实验周均无差异.BMT值4~16周明显高于G2.结论:Cbfα1基因修饰MSCs可刺激骨质疏松大鼠成骨细胞活跃增生,促进骨形成与骨转换速率代谢平衡.并可使骨质疏松大鼠骨组织微观结构改善.%To observe the dynamic changes effects by core-binding factorα1 (Cbfα1 )gene modi-fied marrow mesenchymal stem cells(MSCs) on histomorphometry of postmenopausal osteoporosis(PMOP) with stimulation of bone formation,to study the gene therapy mechanism for PMOP, Methodd: Fifty-four female SD rats were randomly divided into 3 groups: each group was administration for implant Cbfa: gene-modified with MSCs (Groups 1,G1) and ovariectomized (Groups 2,G2) and sharn-ov (Groups 3, G3). Laboretory week was hypothesized by within 4-15 weeks. Observed bone formation signalize: bone osteocalin (BGP); Serum bone specific alkeliphos-phatase (bone AKP) and total alkeliphoshatase (AKP). Bone resorption signalize: urine pyridinoline (PYD) and de-oxypyridinoline (DPD). Bone histomorphometry was measured with whole automobile imaging analysis system, It was examined by biomechanical test (BMT) at 4~16 weeks postoperatively. Results: By the 4~16 weeks after ad-ministration, BGP and bone AKP began to increase, compared with G2 was improved significantly, but PYD and DYD level were no significantly decreased in ovariectomixed at G2 than G1, and bony histomorphometry began to change grodually 4 ~ 16 week in G1. improved in bone formation signal such as trabecular bone volume (TBV) and formation surfase (FS), BMT etc. Conclusion: These results demonstrate that Cbfα: gene modified MSCs mainly influences for increased of bone formation, which might be related to highter stimulate bone cells and lead to the change of the shape of bone,

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