α-硫辛酸联合神经生长因子可促进股骨骨折的愈合

Alpha-lipoic acid and nerve growth factor promote healing of femoral fracture

背景:骨折愈合过程中,除需要适当的生物力学环境外,细胞因子的作用也日益引起重视。目的:观察神经生长因子联合α-硫辛酸治疗对大鼠股骨骨折愈合的影响。方法:建立SD大鼠股骨骨折模型,将72只大鼠随机分为3组:对照组肌肉注射生理盐水;神经生长因子治疗组肌肉注射神经生长因子200 ng/kg,1次/d;联合治疗组肌肉注射神经生长因子200 ng/kg,口服α-硫辛酸25 mg/kg,1次/d。给药后1,2,3周测量骨痂体积,ELISA检测血清骨形态发生蛋白2水平,Western blot检测骨折断端骨形态发生蛋白2蛋白的表达,半定量RT-PCR检测血管内皮生长因子m RNA的表达。结果与结论:(1)给药后1周,3组间骨痂量无明显差异,神经生长因子治疗组和联合治疗组血清骨形态发生蛋白2水平、骨折断端骨形态发生蛋白2蛋白表达、血管内皮生长因子m RNA表达均明显高于对照组(P<0.05),但两组间差异无显著性意义;(2)给药后2周,神经生长因子治疗组和联合治疗组骨痂量、血清骨形态发生蛋白2水平、骨折断端骨形态发生蛋白2蛋白表达、血管内皮生长因子mR NA水平均明显高于对照组(P<0.05),而且联合组高于神经生长因子治疗组(P<0.05);(3)给药后3周,神经生长因子治疗组血清骨形态发生蛋白2水平、骨折断端骨形态发生蛋白2蛋白表达、血管内皮生长因子mRNA明显下降,但联合治疗组仍维持较高水平,明显高于神经生长因子治疗组(P<0.05);(4)结果表明,神经生长因子联合α-硫辛酸比单纯神经生长因子对大鼠股骨骨折愈合的治疗作用更明显。

BACKGROUND： During fracture healing, in addition to the need for appropriate biomechanical environment, the role of cytokines is also increasingly attracted attention. OBJECTIVE： To study the effect of nerve growth factor and alpha-lipoic acid on fracture healing in rat models of femoral fracture.METHODS： Sprague-Dawley rat models of femoral fracture were established. Seventy-two rats were randomly divided into three groups. In the control group, rats were intramuscularly injected with physiological saline. In the nerve growth factor group, rats were intramuscularly injected with nerve growth factor 200 ng/kg, once a day. In the combined therapy group, rats were intramuscularly injected with nerve growth factor 200 ng/kg and orally taken alpha-lipoic acid 25 mg/kg, once a day. At 1, 2 and 3 weeks after administration, bony callus volume was measured. Enzyme linked immunosorbent assay was used to measure serum bone morphogenetic protein-2 levels. Western blot assay was utilized to detect bone morphogenetic protein-2 protein expression at the broken end of fracture. Semi-quantitative RT-PCR was applied to examine vascular endothelial growth factor mR NA expression. RESULTS AND CONCLUSION：（1） At 1 week after administration, no significant difference in bony callus volume was detected among the three groups. Serum bone morphogenetic protein-2 level, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor m RNA expression were significantly higher in the nerve growth factor group and combined therapy group compared with the control group（P〈0.05）, but no significant difference was found between the two groups.（2） At 2 weeks after administration, the amount of callus, serum bone morphogenetic protein-2 levels, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor mR NA levels were significantly higher in the nerve growth factor group and combined therapy group compared with the control group（P〈0.05）. Above expression levels were higher in the combined therapy group than in the nerve growth factor group（P〈0.05）.（3） At 3 weeks after administration, serum bone morphogenetic protein-2 levels, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor m RNA levels were significantly decreased in the nerve growth factor group. However, above expression levels were still high in the combined therapy group, and significantly higher than in the nerve growth factor group（P〈0.05）.（4） These results indicate that nerve growth factor combined with alpha-lipoic acid had better effects on the fracture healing compared with the nerve growth factor alone.