创伤性脑损伤影响骨折愈合速度的机制

A study on the mechanism of traumatic brain injury affecting the speed of bone fracture healing

目的探讨创伤性脑损伤影响骨折愈合速度的可能机制。方法采用创伤性脑损伤合并一侧胫骨骨折(A组)制作多发伤模型,不同时点观察FOS、JUN、bFGF、VEGF表达并与B组(单纯一侧胫骨骨折)比较,X线观察骨折愈合情况。结果正常小鼠脑组织FOS、JUN、bFGF、VEGF低水平表达,B组略强。A组脑组织FOS和JUN的表达具有时程的一致性,创伤性脑损伤(TBI)后3 h达到高峰,12 h以后降至对照水平;bFGF与VEGF分别于创伤性脑损伤后12 h、24 h达到高峰,72 h降至对照水平。两组骨折位点FOS、JUN表达均于6 h达峰值,24 h后降至对照水平。3 h、6 h、12 h组间比较差异有显著性。A组骨折位点bFGF、VEGF表达分别于12 h、24 h达峰值,B组于2,4 h、48 h达峰值,均持续表达96 h以上。Spearman等级相关分析发现,A组脑挫伤灶周围脑组织FOS蛋白与bFGF表达、bFGF与VEGF蛋白表达呈正相关,相关系数分别是0.896、0.832(P<0.05);A组骨折位点FOS蛋白与bFGF表达、bFGF与VEGF蛋白表达呈正相关,相关系数分别是0.938、0.945(P<0.05);B组骨折位点FOS蛋白与bFGF表达、bFGF与VEGF蛋白表达也呈正相关,相关系数分别是0.833、0.914(P<0.05);两组脑组织FOS、JUN蛋白与骨折位点FOS、JUN表达的关系无统计学意义。影像学上A组在术后第三周时已接近全部愈合,B组到第4周时才全部愈合。结论创伤性脑损伤合并长骨骨折足比较理想的多发伤实验动物模型;创伤性脑损伤后骨折位点bFGF、VEGF表达更早更强,促进成骨。

Objective To evaluate the possible mechanism of traumatic brain injury （TBI） affecting the speed of bone fracture healing. Method TBI combined with unilateral tibial fracture （group A） was used to build multiple injury model and simple unilateral tibial fracture （group B）, and the FOS, JUN, bFGF, and VEGF protein expression in different time points between the two groups were compared, and roentgenogram was used for the evaluation of bone healing. Results The expression of FOS, JUN, bFGF, and VEGF protein of the cerebral tissue was low in the normal rats, but was slightly enhanced in group B. There was consistence of development for FOS and JUN expression in the brain tissue in group A, reaching peak at post - TBI 3 hours, and then reducing to control level after 12 hours. The bFGF and VEGF reached peak at post-TBl 12 hours and 24 hours and reduced to control level after 72 hours, respectively. In group A and group B, an increase in the FOS, JUN protein expression around the fracture site was observed at 3 hours after injury, which reached the peak at 6 hours, and reduced to the control level after 24 hours; the comparison between group A, group B and the control group at 3 hours, 6 hours and 12 hours had significant difference （P 〈 0.05）, the pairwise comparison between these 3 time points had significant differences （P 〈 0.05）. In group A, the bFGF and VEGF expression at the bone fracture site reached peak at 12 hours and 24 hours and those in group B reached peak at 24 hours and 48 hours, lasting for more than 96 hours respectively. Spearman rank analysis revealed that there was a positive correlation between the FOS and bFGF, as well as bFGF and VEGF expression around the injured brain lesion in group A with correlation coefficient for 0. 896, 0.832, respectively （ P 〈 0.05 ）, around the fracture site with correlation coefficient for 0.938, 0.945, respectively （P 〈 0.05）. In group B, the FOS and bFGF, bFGF and VEGF expression around the fracture site had positive correlation with correlation coefficient for 0.833, 0.914 respectively （ P 〈 0.05）. The expression correlation of FOS, JUN protein between the brain and the fracture site had no statistical significance. Conclusions TBI makes a stronger and earlier bFGF and VEGF expression at the bone fracture site, thus promoting the osteogenesis.