辛伐他汀对大鼠胫骨骨折愈合的促进作用及其相关信号通路研究

Study on the Promoting Effect of Simvastatin on the tibial fracture healing of Rat and its related Signaling Pathway

关键词:  胫骨骨折  辛伐他汀  核因子κB受体活化因子配体

Key words:  tibial fracture  simvastatin  nuclear factor κB receptor activating factor ligand

摘要:

目的 探讨辛伐他汀对大鼠胫骨骨折愈合的促进作用及其相关信号通路。方法 建立64只SD大鼠右侧胫骨骨折模型，随机分为短期用药组、渐撤量给药组、连续用药组和对照组。术后第1，2，3，4周，每组随机选择4只大鼠处死，分别从X线检查、骨组织HE染色、血清RANKL、OPG水平分析差异。结果 X线检查：术后4周，渐撤量给药组与连续用药组骨折线愈合良好，仅有少量骨痂残留；短期用药组仍可见明显骨痂及骨折线。骨组织HE染色：术后2周，用药组可见编制样骨开始形成，并可见造血细胞灶；术后4周，短期用药组有板层样骨形成，但骨排列方向紊乱，渐撤量给药组可见骨基质中大量骨细胞沉积。血清RANKL水平：术后2周，短期用药组血清RANKL水平明显低于对照组（P<0.05）；连续用药组血清RANKL水平随时间逐渐下降的趋势最明显；术后第3周，短期用药组血清RANKL水平达到峰值，显著高于其他3组。血清OPG水平：术后第2周，各用药组血清OPG水平显著高于对照组（P<0.05），术后第4周，短期用药组血清OPG水平最高（P<0.05）。结论 辛伐他汀对骨折愈合有一定的促进作用，但骤然停药对骨折愈合会造成明显的不良影响。

Abstract:

OBJECTIVE To investigate the promoting effect of simvastatin on tibia fracture healing in rats and its related signal pathway. METHODS The right tibia fracture model of 64 male SD rats was established and divided into short-term group, gradual withdrawal group, continuous group and control group according to the different administration of simvastatin. At 4 time points of 1, 2, 3, 4 weeks after operation, 4 rats in each group were randomly selected and killed. X-ray examination, bone tissue HE staining and serum RANKL,OPG level were used to analyze the difference. RESULTS X-ray examination:4 weeks after operation, the healing of the gradual withdrawal group and the fracture line of the continuous medication was good, with only a small amount of residual bone residual. The short-term group was still visible bone fracture and fracture line. HE staining of bone tissue:2 weeks after operation, the prepared bone began to form and hematopoietic cell foci could be seen in the treatment group. At 4 weeks after operation, lamellar bone formation was found in the short-term group, but the direction of bone arrangement was disordered. A large number of bone cells were deposited in the bone matrix in the gradual withdrawal group. The level of serum RANKL in the short-term group was significantly lower than that in the control group after 2 weeks of operation(P<0.05). The trend of serum RANKL gradually decreasing with time in the continuous group was the most obvious. In the third week after operation, the short-term group peaked significantly higher than the other three groups. The level of serum OPG in the treatment group was significantly higher than that in the control group at the 2nd week after operation(P<0.05). and the level of serum OPG in the short-term group was higher than that in other group at the 4th week after operation(P<0.05). CONCLUSION Simvastatin has a certain effect on the healing of the fracture, but the sudden drug withdrawal can have a significant adverse effect on the fracture healing.