糖尿病兔桡骨骨缺损应用生物陶瓷人工骨修复的生物体视学研究

Biological stereology study of bioceramic artificial bone repair on radial bone defect in diabetic rabbits

目的运用生物体视学方法探讨糖尿病对人工骨修复骨缺损过程及对新生骨爬行替代的影响。方法选取体重2.0耀2.5 kg的健康雄性新西兰大白兔24只,随机分成正常组及糖尿病组,每组12只。糖尿病组使用2%的四氧嘧啶按100 mg/kg经耳缘静脉注射途径给药,两周后空腹血糖持续>16.0 mmol/L作为建模成功的标准,对照组则经耳缘静脉注入等量生理盐水。两组均制作双侧桡骨中段1.5 cm长的标准骨缺损模型,于骨缺损处植入钙磷生物陶瓷人工骨。术后4、8、12周分别处死兔子后取材制作硬组织切片,检测骨组织微结构及血管体视学密度参数。结果糖尿病组造模后血糖浓度大于16.0 mmol/L。术后4、8、12周,两组%Tb.Ar、Tb.Th、Tb.N均升高,Tb.Sp降低,且糖尿病组优于正常组(P<0.05)。术后4、8、12周,两组Lv、Sv、Vv均不同程度地升高,且糖尿病组Lv、Sv均显著低于正常组,差异显著(P<0.05);术后8、12周,糖尿病组Vv低于正常组(P<0.05)。结论使用2% 100 mg/kg四氧嘧啶给药能够获得良好的糖尿病兔模型;生物体视学研究发现,钙磷生物陶瓷人工骨能够诱导成骨,而糖尿病影响其成骨效应,糖尿病可能影响生物陶瓷人工骨的降解及新生骨爬行替代过程,进而影响骨缺损的修复。

Objective To investigate the effect of diabetes mellitus on artificial bone repair of bone defects and the creeping substitution of new bone by using biological stereology method.Methods Twenty-four healthy male 2.0-2.5 kg white rabbits from New Zealand were randomly divided into normal group and diabetic group, with 12 rabbits in each group. The diabetic group received 2% alloxan 100 mg/kg via auricular vein injection route. Two weeks later, the fasting blood glucose16.0 mmol/L was used as the standard for modeling success, while the control group was injected with the same amount of normal saline through the auricular vein. The standard bone defect model of 1.5 cm length in the middle of bilateral tibia was made in both groups, and the calcium-phosphorus bioceramic artificial bone were implanted in bone defect. After 4, 8 and 12 weeks, rabbits were sacrificed respectively, and then hard tissue sections were made to detect the microstructure of bone tissue and the parameters of vascular stereological density.Results The blood glucose concentration of the diabetic group was higher than 16.0 mmol/L. At 4, 8 and 12 weeks after surgery, the levels of %Tb.Ar, Tb.Th and Tb.N increased, level of Tb.Sp decreased in both groups, and those in the diabetic group were better than the normal group（P〈0.05）. At 4, 8 and 12 weeks after surgery, the levels of Lv, Sv and Vv in the two groups increased to varying degrees,and the levels of Lv and Sv in the diabetic group were significantly lower than those in the normal group（P〈0.05）; at 8 and 12 weeks after surgery, Vv level in the diabetic group was lower than that in the normal group（P〈0.05）.Conclusion Using 2% 100 mg/kg alloxan can obtain a good diabetic rabbit model. Biological stereological studies shows that calcium-phosphorus bioceramic artificial bone can induce osteogenesis, while the diabetes will affect its osteogenic effect, diabetes may affect the degradation of bioceramic artificial bone and the process of creeping replacement of new bone, and then affect the repair of bone defect.