rhBMP_2不同动物异位诱导成骨及其小鼠体内诱导成骨的剂量依赖性

目的对大肠杆菌表达的hBMP2在小鼠体内进行剂量依赖性研究,并观察其在大鼠和家兔体内异位诱导成骨情况,为临床应用提供参考。方法大鼠、家兔股部肌袋植入rhBMP21.5和3.0mg,植入后1、2、4周取材观察成骨情况;小鼠股部肌袋植入100~1000μg的rhBMP2,植入后1、2、3周取材,行组织学检查,成骨量分析,碱性磷酸酶和钙含量测定。结果大鼠植入1.5mgrhBMP2植入2周、家兔3.0mgrhBMP2植入4周表现为高效成骨活性。rhBMP2小鼠体内诱导成骨实验表现为成骨量,碱性磷酸酶活性和钙含量显著的剂量依赖性。结论原核表达的hBMP在小鼠、大鼠和家兔体内有高效的诱导成骨活性,小鼠体内实验rhBMP2表现为明显的剂量依赖性。

The ectopic bone formation activity of rhBMP-2 in different animals and its dose dependent effect in mice

Objective:To investigate the dose dependence of rhBMP-2 expression in E.coli in mice and to abserve the bone inductive activity in rats and rabbits.Methods:1.5 and 3.0 mg rhBMP-2 were implanted into the thigh muscle pouches of rats and rabbits.The rats and rabbits were sacrificed after 1, 2 and 4 weeks to observe histologically whether there were cartilage and bone formation. 100-1000μg rhBMP-2 were implanted into thigh muscle pouches of mice, The mice were sacrificed after day 7,14 and 21,then the induced ectopic bone formation was studied by histological analysis,the quantity of new bone,the ALP activity levels and calcium content measurement.Results: 2 weeks after implantation in rats,4 weeks in rabbits, 1.5mg and 3.0 mg rhBMP-2 showed obvious bone formation activity.The expriment induced bone formation in mice showed that the quantity of new bone,the ALP activity levels and calcium content significantly correlated with the rhBMP-2 dosage. Conclution:The rhBMP-2 expressed in E.coli manifested high bong-inductive activity in rats and rabbits,and significant dose-dependence was shown in mice.