持续动态压应力对实验性骨折愈合的影响及相关信号转导通路研究  

Effect of continuous dynamic pressure stress on experimental fracture healing and exploration of related signaling transduction pathways

作　　者：任可[1] 张春才[2] 赵建宁[1] 汪光晔 陆维举[1] 陈勇[1] 孙剑伟[2] 

机构地区：[1]南京军区南京总医院骨科,南京210002 [2]第二军医大学附属长海医院骨科,上海200433 [3]芜湖市中医院骨科,芜湖241000

出　　处：《中国矫形外科杂志》2010年第4期327-332,共6页Orthopedic Journal of China

摘　　要：[目的]探讨持续动态压应力环境对实验性骨折愈合的影响及环氧化酶-2(cyclooxygenase,COX-2)、前列腺素E2(prostaglandin E2,PGE2)和环磷酸腺苷(cyclic adenosine monophosphate,cAMP)这一信号通路是否参与了该调控过程。[方法]120只新西兰兔行单侧肱骨干截骨,A、C两组以形状记忆接骨器内固定,B组以加压钢板固定,且术后C组以3 mg.kg-1.d-1的Celecoxib灌胃。术后定期在骨折间隙处取材并留取血清标本,用Real-time RT-PCR测定COX-1、COX-2基因转录水平,以放射免疫法测定PGE2、cAMP含量,观察愈合骨痂的组织学改变并检测血清中骨特异性碱性磷酸酶和骨钙素活性。[结果]各组COX-2转录水平以及PGE2、cAMP的含量均随愈合过程呈显著改变,且随内固定方式表现出明显差异。组织学和血清学结果则显示A组骨折间隙内软骨内成骨和编织骨痂的改建均领先于B组,而抑制形状记忆接骨器内固定下增高的COX-2活性后骨折愈合的组织学过程变缓,血中成骨特异性蛋白水平也明显下降。[结论]形状记忆接骨器产生的持续动态压应力环境可以促进软骨内成骨及随后的骨痂塑形,加速骨折愈合,而且该效应与COX-2、PGE2、cAMP这一信号转导通路密切相关。[Objective]To evaluate the effect of continuous dynamic pressure stress on experimental humeral fracture healing and to explore the role of COX-2 /PGE2 /cAMP signaling pathway in healing promotion induced by the special biomechanical condition.[Method]A total of 120 New Zealand rabbits were divided randomly into three groups： Group A,unilateral humeral fracture was fixed with shape memory connector（SMC）,producing axial continuous dynamic pressure stress on fracture gap.Group B,fixed with 4-hole DCP,and Group C,fixed with SMC and gavaged with aqueous suspensions of celecoxib（3 mg/kg/day） after fracture.COX-1 and COX-2 mRNA expressions in fracture gap were determined by real-time RT-PCR at 0,3,7,14,21,28 and 56 days after operation,as well as the contents of PGE2 and cAMP were measured by radioimmunoassay（RIA）.Bone-specific alkaline phosphatase（B-ALP） activity was determined by measuring p-nitrophenol and osteocalcin concentrations were measured using enzyme-linked immunosorbent assay（ELISA） for serial collected blood samples.Callus specimens fixed by formalin were used for histopathological examination.[Result]The COX-2 mRNA levels normalized with GAPDH mRNA as well as the contents of PGE2 and cAMP showed significant difference along with the 56-day period and also between the two internal fixations.Histopathological observation and determination of serum biochemical markers of bone formation revealed that the endochondral bone formation and the callus remodelling took place earlier in Group A than in Group B.The accelerated healing process and increased serum values of the bone formation markers induced by continuous dynamic pressure stress of SMC were inhibited by celecoxib,a specific COX-2 inhibitor.[Conclusion]The persistent dynamic longitudinal pressure stress produced by SMC contributed to endochondral bone formation and callus remodelling,resulting in an acceleration of fracture healing,which was considered to be closely correlated with the COX-2/PGE2/cAMP signal transduction pathway.

关 键 词：骨折内固定术 骨折愈合 应力 环氧化酶 形状记忆合金 

分 类 号：R683[医药卫生—骨科学]