合并脑损伤时骨折愈合过程中血管内皮细胞生长因子的表达

背景：大量临床病例显示，骨折合并脑损伤患者骨痂量明显增多，骨折愈合速度明显加快。但对合并脑损伤时骨折愈合过程中血管内皮细胞生长因子的表达及作用机制缺乏前瞻性对照研究，对其潜在的机制尚未阐明。目的：对比观察SD大鼠在骨折合并脑损伤以及单纯骨折时骨折愈合过程中骨痂内血管内皮细胞生长因子的表达变化。方法：将SD大鼠以数字表法随机分为3组：正常对照组、单纯骨折组、骨折合并脑损伤组。脑损伤模型采用改进的Marmarou自由落体装置撞击大鼠颅骨制作弥漫性中度脑损伤模型；于左侧胫骨髁间处钻孔，插入无菌克氏钢针，在胫骨中上1/3处横向折断胫骨，制作骨折模型。术后X射线摄片观察骨折修复过程和效果；RT-PCR检及免疫组化染色观察骨痂标本血管内皮细胞生长因子表达。结果与结论：骨折后3，7，14 d，单纯骨折组、骨折合并脑损伤组X射线表现无明显差别。与单纯骨折组相比，骨折后 24 d脑损伤合并骨折组骨折线变得模糊，形成较多骨痂量；42 d后骨折线消失，伤肢基本愈合。单纯骨折组骨痂中血管内皮细胞生长因子骨折后7 d开始出现，表达逐渐增强，约3周时达高峰，42 d已经不见血管内皮细胞生长因子表达；脑损伤合并骨折后3 d即可见血管内皮细胞生长因子表达，两三周达高峰期，其表达高峰提前且持续时间较长。说明脑损伤后大鼠骨折愈合加速，骨痂量增多，表明脑损伤对骨折愈合有促进作用，这可能与脑损伤后大鼠体内生长因子血管内皮细胞生长因子表达高峰提前且持续时间较长有关。

Expression of vascular endothelial growth factor in fracture healing rats combined with brain injury

BACKGROUND: Many clinical cases demonstrated that the callus number was obvious increased, and the bone healing was faster in fracture patients combined with brain injury. However, there is not a prospective control study underlying the effects of vascular endothelial growth factor (VEGF), and the mechanism is unclearly. OBJECTIVE: To explore the changes of VEGF expression in SD rats fracture healing combined with brain injury and fracture only. METHODS: SD rats were randomly divided into 3 groups: normal control, simple fracture and fracture combined with brain injury groups. Rat diffuse midrange brain injured model was prepared by using modified Marmarou installation method. In addition, rat fracture model was prepared as follow: Knee joint of left lower extremity was depilated and sterilized, Condyles of tibia was perforated, shin bone was fracted transversally in above 1/3 of shin bone. The reparative process and effect of fracture were observed by X-ray films; and VEGF expression in the Osteotylus samples were detected by RT-PCR and immunohistochemistry staining.RESULTS AND CONCLUSION: There were no obviously differences between the simple fracture and fracture combined with brain injury groups at days 3, 7 and 14 after fracture. Compared to the simple fracture group, the fracture lines of the brain injury combined fracture group have become blurred, and formed a great quantity osteotylus surrounding the fracture parts at day 24, and the fracture lines disappeared after 42 days, the fracture has basically healed. In the simple fracture group, the expression of VEGF appeared at day 7, gradually increased, reached a peak at week 3, but disappeared after 42 days. In the brain injury combined fracture group, the expression of VEGF appeared at day 3, and reached a peak 2-3 weeks later. Its peak expression was early and lasted for a longer time. It demonstrated that the bone healing was faster in fracture rat combined with brain injury, namely, brain injury has promoted effect on fracture healing, which may relevant to longer persistence time and ahead of schedule of VEGF expression.