血清bFGF、TGF-β、VEGF的高表达有助于大鼠脑外伤合并肢体骨折的快速愈合

The Expression Level of Serum bFGF, TGF-β and VEGF could Accelerate the Healing Progress for Rats with Brain Injury Combined with Limb Fracture

为揭示脑外伤对血清bFGF、TGF-β、VEGF表达和肢体骨折愈合速度的影响机制，本研究选择SD大鼠作为研究对象，分别建立中等程度脑外伤模型和股骨骨折模型，将大鼠分为A组（正常对照）、B组（单纯股骨骨折）、C组（单纯脑外伤）和D组（脑外伤合并股骨骨折），每组25只，分别检测手术前0d及手术后3d、7d、15d和30d时的血清bFGF、TGF-β和VEGF水平，并考察不同时间点骨折愈合情况。结果发现，B组在术后3d时bFGF、TGF-β和VEGF水平迅速达到高峰，此后逐渐降低。而C组和D组的三种细胞因子水平变化趋势类似，均在术后15d时达到最高。组间比较显示，D组大鼠在术后3～30d期间内bFGF水平显著高于C组，并且在7d、15d和30d时bFGF水平高于B组。D组在7d、15d和30d时的TGF-β水平显著高于B组和C组。D组在15d和30d时的VEGF水平显著高于B组和C组。并且，D组3种生长因子在整个实验期间的最高值均显著高于其他组。HE染色结果显示，脑外伤合并骨折的大鼠其肉芽组织、成纤维细胞、骨小梁、板层骨形成速率均显著高于单纯骨折大鼠，而X线显示该组骨痂量和密度明显高于单纯骨折组。本研究的结果说明，脑外伤合并股骨骨折大鼠的bFGF、TGF-β和VEGF水平显著高于单纯脑外伤或股骨骨折大鼠，并且其骨折愈合速度也更快。bFGF、TGF-β和VEGF水平均可在脑外伤和骨折大鼠血清中高度表达，而脑外伤的发生可能通过改变bFGF、TGF-β和VEGF等生长因子水平，从而间接促进大鼠自身的骨折愈合，本研究的成果可作为临床骨科治疗研究的借鉴与参考。

To reveal the effects of brain injury on the expression of serum bFGF, TGF-β, VEGF and the healing rate of limb fracture, SD rats were selected as the study subjects and established moderate brain injury model and femur fracture model separately. Rats were divided into group A （normal control）, group B （simple femoral fracture）, group C （simple brain trauma） and Group D （brain trauma combined with femoral fracture）, 25 rats in each group and serum level of bFGF, TGF-β and VEGF were tested at 0 d before surgery and 3 d, 7 d, 15 d and 30 d after surgery. Fracture healing situation at different time points were checked at the mean time. It was found that the levels of bFGF, TGF-β and VEGF in group B peaked rapidly at 3 d after surgery and gradually decreased thereafter. The changes of the three cytokine levels in group C and group D were similar that reached the highest at 15 d after surgery. The comparison between groups showed that the bFGF level in group D was significantly higher than that in group C during 3-30 d after operation, and bFGF level was higher than group B at 7 d, 15 d and 30 d. The levels of TGF-β in group D at 7 d, 15 d and 30 d were significantly higher than those in groups B and C. The levels of VEGF in group D at 15 d and 30 d were significantly higher than those in groups B and C. Moreover, the highest values of the three growth factors in group D were significantly higher than in the other groups during the whole experiment. The results of HE staining showed that the rate of granulation tissue, fibroblasts, trabecular bone and lamellar bone formation in rats with traumatic brain injury and fracture was significantly higher than that in simple fractured rats, while X-ray showed that the amount and density of osteophytes in this group were obviously higher than the simple fracture group. It could be indicated in this study that the levels ofbFGF, TGF-β and VEGF in rats with traumatic brain injury and femoral fracture were significantly higher than those in rats with brain trauma or femur fracture, and the fracture healing rate was also faster. The levels of bFGF, TGF-β and VEGF can be highly expressed in the serum of rats with traumatic brain injury and fracture, and the occurrence of brain trauma may indirectly promote the fracture healing of rats by changing the levels of growth factors such as bFGF, TGF-β and VEGF. The results of this study could be used as a reference for clinical department of orthopedics research.