低相对分子质量肝素对老年大鼠骨质疏松性骨折愈合过程的影响

The effects of low molecular weight heparin on fracture healing in aged osteoporotic rats

目的探讨低相对分子质量肝素(LMWH)对老年大鼠骨质疏松性骨折愈合过程的影响。方法老年雄性SD大鼠60只,制成左股骨骨折模型,随机分为对照组和LMWH组,LMWH组于术后即刻给予LMWH100U·kg-1·d-1,共10d。两组均在术后不同时间段取骨痂,行苏木素-伊红(HE)染色、转化生长因子(TGF)-β1免疫组织化学染色,测骨密度、血清碱性磷酸酶(ALP),12周行放射学观察。结果①组织学观察:HE染色,LMWH组软骨内成骨过程较对照组延迟;TGF-β1免疫组织化学染色,LMWH组在1、2、3和4周TGF-β1阳性表达的积分吸光度值均弱于对照组,差异有统计学意义;②骨密度:LMWH组4、8和12周骨痂骨密度均低于对照组,差异有统计学意义;③血清ALP:LMWH组低于对照组,差异有统计学意义;④放射学观察:LMWH组术后12周骨折线仍较清晰,断端骨痂连接不紧密。结论LMWH通过抑制TGF-β1的表达,延缓老年大鼠骨质疏松性骨折的愈合。

Objective To investigate the effects of low molecular weight heparin （LMWH） on fracture healing in aged osteoporotic rats. Methods Fracture healing model was established on left femur in 60 aged male rats, which were randomized into two groups （LMWH and control groups）. The LMWH group was given daily subcutaneous injection of 100 U/kg LMWH for a total of 10 days. The rats were scarified at different weeks after operation, The callus formation was assessed with HE-stained histology and TGF-β1 immunohistochemistry （IHC）. The bone minerai density （BMD） was measured, and alkaline phosphatase （ALP） activity as an index of bone formation was determined. Normal radiographs were taken at 12 weeks. Results （1）Histomorphological analysis revealed that the process of cartilage forming and transforming were delayed in the LMWH group. The IHC results showed decreased TGF-β1 expression in the LMWH group at weeks 1, 2, 3 and 4 as compared with controls. （2）At weeks 4, 8 and 12, the LMWH group showed lower BMD of callus. （3）LMWH produced a significant decrease in serum ALP. （4）Normal radiographs showed that LMWH group had less callus formation. Conclusion LMWH was shown to delay the fracture healing in aged osteo- porotic rats through inhibition of TGF-β1.