加减桃红四物汤联合神经生长因子对肋骨骨折大鼠骨折愈合的影响

Effect of Modified Taohong Siwu Decoction Combined with Nerve Growth Factor on Rid Fracture Healing in Rats

目的探讨加减桃红四物汤联合神经生长因子对肋骨骨折大鼠骨折愈合的影响。方法将60只健康6个月龄无特定病原雌性Sprague Dawley(SD)大鼠采用随机数字表法分为神经生长因子组、桃红四物汤组、神经生长因子联合桃红四物汤组(联合组)、模型组及空白组,每组各12只。造模完成后第2天开始给药,神经生长因子组每天给予2 ml生理盐水稀释神经生长因子并在骨折断端处注射0.2 ml;桃红四物汤组给予桃红四物汤灌胃,根据人鼠体表面积换算为1.85 g/kg;联合组给予2 ml/d生理盐水稀释神经生长因子并在骨折断端处注射0.2 ml,同时加桃红四物汤灌胃1.85 g/kg;模型组及空白组均按照1.85 g/kg灌服蒸馏水,1次/d,连续给药14 d。观察比较给药7 d后、给药14 d后各组大鼠骨组织形态、骨折愈合情况、骨密度及骨矿物质含量、血浆骨形态发生蛋白2(Bone morphogenetic protein-2,BMP-2)、血管内皮生殖因子(Vascular endothelial growth factor,VEGF)、血清骨保护素(Osteoprotegerin,OPG)、核因子kappaB受体活化因子配体(Receptor activator of nuclear factor kappa B ligand,RANKL)水平。结果与模型组同期比较,联合组、神经生长因子组、桃红四物汤组骨小梁宽度、骨小梁成骨指数均明显升高,差异有统计学意义(P<0.05);联合组骨小梁宽度、骨小梁成骨指数均高于神经生长因子组、桃红四物汤组同期,差异有统计学意义(P<0.05)。与模型组同期比较,神经生长因子组、桃红四物汤组、联合组骨体积分、骨痂总体积、骨痂总面积均明显升高,差异有统计学意义(P<0.05);联合组骨体积分、骨痂总体积、骨痂总面积均明显高于神经生长因子组、桃红四物汤组同期,差异有统计学意义(P<0.05)。与模型组同期比较,神经生长因子组、桃红四物汤组、联合组骨密度、骨矿物质含量均明显升高,差异有统计学意义(P<0.05);联合组骨密度、骨矿物质含量均高于神经生长因子组、桃红四物汤组同期,差异有统计学意义(P<0.05)。与模型组同期比较,神经生长因子组、桃红四物汤组、联合组BMP-2、VEGF、OPG、RANKL含量均明显升高,差异有统计学意义(P<0.05);联合组BMP-2、VEGF、OPG、RANKL含量均高于神经生长因子组、桃红四物汤组同期,差异有统计学意义(P<0.05)。结论加减桃红四物汤联合神经生长因子能够有效促进肋骨骨折大鼠骨折愈合,其机制可能与调节BMP-2、VEGF、OPG、RANKL含量相关。

Objective To investigate the impact of modified Taohong Siwu Decoction combined with nerve growth factor on rib fracture healing in rats.Method Sixty healthy 6-month-old female Sprague Dawley(SD)rats were ran-domly divided into the Nerve Growth Factor group,Taohong Siwu Decoction group,Combined group(Nerve Growth Factor+Taohong Siwu Decoction),Model group,and Blank group,with 12 rats in each group.Medication started on the second day after modeling.In the Nerve Growth Factor group,2 ml of physiological saline diluted Nerve Growth Factor was admin-istered daily,with an injection of 0.2 ml at the fracture site.The Taohong Siwu Decoction group received Taohong Siwu De-coction by gastric lavage at a dose of 1.85 g/kg based on body surface area conversion.The Combined group received both Nerve Growth Factor and Taohong Siwu Decoction,with the same dosages as the respective mono-therapy groups.The Model and Blank groups received distilled water at a dose of 1.85 g/kg by gastric lavage once a day for 14 days.After 7 and 14 days of treatment,the bone tissue morphology,fracture healing status,bone density,bone mineral content,plasma levels of Bone Morphogenetic Protein-2(BMP-2),vascular endothelial growth factor(VEGF),osteoprotegerin(OPG),and receptor activator of nuclear factor kappa B ligand(RANKL)were observed and compared among the groups.Re-sults Compared with the Model group,the Combined group,Nerve Growth Factor group,and Taohong Siwu Decoction group showed significant increases in trabecular width and trabecular bone formation index,with statistical significance(P<0.05).The Combined group had higher trabecular width and trabecular bone formation index than the Nerve Growth Factor group and Taohong Siwu Decoction group at the same time points,with statistical significance(P<0.05).In com-parison with the Model group,the Nerve Growth Factor group,Taohong Siwu Decoction group and the Combined group ex-hibited significantly increased bone volume fraction,total callus volume,and total callus area,with statistical significance(P<0.05);the Combined group had higher values of bone volume fraction,total callus volume,and total callus area than the Nerve Growth Factor group and Taohong Siwu Decoction group at the same time points,with statistical significance(P<0.05).When compared with the Model group,the bone density and bone mineral content were significantly increased in the Nerve Growth Factor group,Taohong Siwu Decoction group,and Combined group,with statistical significance(P<0.05);the Combined group had higher bone density and bone mineral content than the Nerve Growth Factor group and Taohong Siwu Decoction group at the same time points,with statistical significance(P<0.05).In comparison with the Model group,the BMP-2,VEGF,OPG,and RANKL levels were significantly increased in the Nerve Growth Factor group,Taohong Siwu Decoction group,and Combined group,with statistical significance(P<0.05);the Combined group had higher levels of BMP-2,VEGF,OPG,and RANKL than the Nerve Growth Factor group and Taohong Siwu Decoction group at the same time points,with statistical significance(P<0.05).Conclusion The combination of modified Taohong Siwu Decoction with Nerve Growth Factor effectively promotes rib fracture healing in rats,possibly by regulating BMP-2,VEGF,OPG,and RANKL levels.