肌肉生长抑制素论文：小鼠骨折后不同时期应用GDF-8抑制剂对其骨折愈合的影响.docVIP

肌肉生长抑制素论文：小鼠骨折后不同时期应用GDF-8抑制剂对其骨折愈合的影响 【中文摘要】Myostatin (GDF-8)肌肉生长抑制素是TGF-β超家族中的一员，骨骼肌生长的负性调控因子。Myostatin在骨骼肌中高度表达，当它功能缺失时会导致骨骼肌量成倍减少。近期研究发现敲除肌肉生长抑制素基因的小鼠表现出骨骼肌量明显增加，整个骨架的强度和矿化增加。Myostatin基因在骨折修复早期即有表达，它的表达程度直接或间接的影响一些重要的促骨折愈合因子的表达。Myostatin基因缺失小鼠已经在研究肌肉再生与骨折愈合的相互作用中有所应用。通过观察小鼠腓骨骨折后不同时间应用GDF-8抑制剂，观察骨折愈合情况，检测骨折处骨痂量及骨密度，探讨其对骨折愈合情况的影响及最佳的用药时间窗，为骨折愈合过程中骨组织和周围组织的修复重建提供一个新的用药途径。方法：4月龄，体重相近，SPF级，雄性BALB/c小鼠60只进行腓骨骨折造模，造模成功的48只小鼠随机均分为造模后应用安慰剂的对照组、造模后不同起始时间腹腔注射相同剂量肌肉生长抑制素抗体的0天组，1周组，2周组，共4组，每组12只，造模后4周测量骨折处骨痂骨密度，测量细胞肌肉生长抑制素含量变化和肌肉组织变化。结果：造模成功率为80%。各组小鼠体重差异无显著性意义(P 0.05)，0天组腓肠肌质量和骨痂骨密度明显高于其他3组(P 0.01)，其他3组比较差异无显著性意义。与其他3组比较，0天组肌肉细胞组织形态及细胞内肌肉生长抑制素含量也有明显差别。结论：造模后及早应用肌肉生长抑制素抑制剂可增加小鼠骨折处骨痂骨密度并促进骨折处肌肉增生。 【英文摘要】BACKGROUND: Myostatin (GDF-8), a member of the transforming growth factor-beta(TGF-β) superfamily of secreted growth and differentiation factors, is a negative regulator ofskeletal muscle growth。It is highly expressed in skeletalmuscle, and myostatin loss-of- functionleads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a modelfor studying muscle-bone interactions. Recent researches have found that myostatin knockoutmice showed a significant increase in muscle mass; the intensity and mineralization of the wholeskeleton increase as well. Myostatin expression is found in the early stage of fracture repair.PURPOSE: To explore the effects of application of myostatin at different stages on the callusamount and bone mineral density of fibula fractures in mice.METHODS: Fibula fracture model was constructed in mice. The 48 model mice were randomlydivided into three groups: control group (empty treatment other than model construction), 0 daygroup, 1 week group and 2 weeks group (mice in the la tter three groups were injected withmyostatin antibody of the same dose at different starting times after model construction). Thecallus amount of the fractures was measured in the 4thweek after model construction. Myostatincontent changes and muscle tissue change