信号选择性甲状旁腺素模拟肽促进去势雄性小鼠的骨折愈合  

Effects of signaling-selective parathyroid hormone peptide analog on fracture healing in orchiectomized mouse models

作　　者：袁亮[1] 林振[1] 付兆宗[1] 孟越[1] 黄志平[1] 吴秀华[1] 杨德鸿[1] 江建明[1] 

机构地区：[1]南方医科大学南方医院脊柱骨科,广东广州510515

出　　处：《南方医科大学学报》2013年第2期182-187,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(30973061);南方医院院长基金(2009A002)~~

摘　　要：目的观察间断皮下注射信号选择性甲状旁腺素(PTH)模拟肽对去势雄性小鼠骨折愈合的影响。方法 36只7周龄C57/BL雄性小鼠去势,1周后制作股骨中段骨折模型,术后用人重组甲状旁腺素(hPTH(1-34)),信号选择性PTH模拟肽[Gly1,Arg19]hPTH(1-34)(G1,R19(1-28))和等量溶解剂注射,于术后14 d和28 d处死,双能X线骨密度仪测量骨痂区骨密度以及骨矿物含量;术侧骨折愈合情况通过X线、显微CT、生物力学和组织学显示。结果术后14 d,G1,R19(1-28)组骨密度显著高于对照组(P<0.05)。最大力和刚度G1,R19(1-28)低于hPTH(1-34)组。X线和显微CT显示,G1,R19(1-28)组骨痂的改建和重塑优于对照组,略差于hPTH(1-34)组。结论信号选择性甲状旁腺素模拟肽G1,R1(91-28)促进骨折的愈合,cAMP/PKA通路对促进骨折愈合具有重要作用。Objective To assess the effect of intermittent subcutaneous injections of signal-selective parathyroid hormone （PTH） peptide analog on fracture healing in orchiectomized mouse models. Methods Thirty-six 7-week-old C57/BL male mice were orchiectomized and injected with hPTH（1-34）, the signal-selective PTH peptide analog [Gly1,Arg^19]hPTH（1-34）, or an identical volume of vehicle 1 week after induction of femoral fracture. At 14 and 28 days after the operation, the mice were sacrificed for measurement of bone mineral density （BMD） and bone mineral content （BMC） of the callus using by dual energy X-ray absorptiometry. The bone healing was evaluated by radiography, biomechanical testing, micro-computed tomography （Micro-CT） and histological examination. Results At 14 days after the operation, BMD in PTH peptide analog group was significantly increased （P〈0.05）. The mouse models treated with the PTH peptide analog showed significantly lower ultimate bending force and bending rigidity than those with hPTH（1-34） treatment. X-ray and Micro-CT scanning showed that callus transformation and remodeling was better in PTH peptide analog group than in the vehicle control group but poorer than in hPTH（1-34） group. Conclusion The signaling-selective PTH peptide analog G1, R^19 （1-28） can accelerate fracture healing in orchiectomized mouse models, in which process cAMP/PKA pathway plays an important role.

关 键 词：甲状旁腺激素 去势 骨折愈合 信号通路 PKA 

分 类 号：R683[医药卫生—骨科学]