间歇性低剂量应用rhPTH（1-34）对兔骨折愈合的影响
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摘要
背景骨折的愈合是个非常复杂的过程,其影响因素也是多方面的,包括骨折局部的血运、年龄和健康状况、医源性因素等。近年来各种生长因子和内分泌因素对骨折愈合影响已成为热门课题。本研究主要就重组人甲状旁腺素1-34片段对小范围骨缺损的促愈合作用进行实验研究,以期发现其对骨折愈合的影响。
目的研究间歇性低剂量应用重组人甲状旁腺素(rhPTH1-34)对兔胫骨小范围骨缺损的治疗作用。
方法50只新西兰大白兔于右侧胫骨中段造成3mm缺损,术后予石膏外固定,随机分成A,B两组。术后第二天A组开始按30μg/(kg·d)行腹部皮下注射,每周3次,共4周.B组按同样方法注射等量生理盐水。术后1、2、3、4周每组随机抽取兔4只处死取材,行X线射片,骨密度(BMD)、骨矿物含量(BMC)测试,BMP-2(骨形态发生蛋白-2)免疫组化染色并观察并且第4周行HE切片染色观察。
结果A组的骨痂面积、成骨细胞含量同期均高于B组。治疗后2组间和组内比较差异均有显著性,2组BMD和BMC在术后随时间延长增加,2、3、4周时A组BMD和BMC高于B组(P<0.05,P<0.01),A组在2、3、4周BMP-2的表达均高于对照组,二者差异有显著性(P﹤0.01).
结论间歇性低剂量应用rhPTH1-34能够促进成骨细胞分化,加速骨矿物沉积,同时诱导BMP-2表达从而加速骨折的愈合.
Objective: To study the effect of intermittent low-dose administration of rhPTH(1-34) on fracture healing.
Methods: A 3 mm gap was performed in right mid-tibials of 50 New Zealand white rabbits.The osteotomy site was stabilized with long plaster cast external fixation.The rabbits were divided randomly into two groups such as A and B group.On the postoperative day,the A group were administrated with rhPTH(1-34) by hypodermic injection,while the B group with NS,3 times a week for 4 weeks.Fracture healing was assessed with X-ray,BMD、BMC test,BMP-2 immunohistochemistry dying.At 4th week of postoperation,histologic analysis was tested with callus and quantity of osteoblast.
Results: Callus,the quantity of osteoblast in the A group were more than the B group.There are difference between two groups and intergroup.BMD and BMC at the 2 groups increased along with times,it was much more in the A group than that in the B group at 2、3、4 week(p<0.05,p<0.01).The expression of BMP-2 in the A group higher than it in the B group at 2、3、4 weeks,showing a significant difference(p<0.01)
Conclusion: Intermittent low-dose administration of rhPTH(1-34) can obviously promote the fracture healing,accelerat the differentiation of osteoblasts、the mineralization of bone and expression of BMP-2.
目的研究间歇性低剂量应用重组人甲状旁腺素(rhPTH1-34)对兔胫骨小范围骨缺损的治疗作用。
方法50只新西兰大白兔于右侧胫骨中段造成3mm缺损,术后予石膏外固定,随机分成A,B两组。术后第二天A组开始按30μg/(kg·d)行腹部皮下注射,每周3次,共4周.B组按同样方法注射等量生理盐水。术后1、2、3、4周每组随机抽取兔4只处死取材,行X线射片,骨密度(BMD)、骨矿物含量(BMC)测试,BMP-2(骨形态发生蛋白-2)免疫组化染色并观察并且第4周行HE切片染色观察。
结果A组的骨痂面积、成骨细胞含量同期均高于B组。治疗后2组间和组内比较差异均有显著性,2组BMD和BMC在术后随时间延长增加,2、3、4周时A组BMD和BMC高于B组(P<0.05,P<0.01),A组在2、3、4周BMP-2的表达均高于对照组,二者差异有显著性(P﹤0.01).
结论间歇性低剂量应用rhPTH1-34能够促进成骨细胞分化,加速骨矿物沉积,同时诱导BMP-2表达从而加速骨折的愈合.
Objective: To study the effect of intermittent low-dose administration of rhPTH(1-34) on fracture healing.
Methods: A 3 mm gap was performed in right mid-tibials of 50 New Zealand white rabbits.The osteotomy site was stabilized with long plaster cast external fixation.The rabbits were divided randomly into two groups such as A and B group.On the postoperative day,the A group were administrated with rhPTH(1-34) by hypodermic injection,while the B group with NS,3 times a week for 4 weeks.Fracture healing was assessed with X-ray,BMD、BMC test,BMP-2 immunohistochemistry dying.At 4th week of postoperation,histologic analysis was tested with callus and quantity of osteoblast.
Results: Callus,the quantity of osteoblast in the A group were more than the B group.There are difference between two groups and intergroup.BMD and BMC at the 2 groups increased along with times,it was much more in the A group than that in the B group at 2、3、4 week(p<0.05,p<0.01).The expression of BMP-2 in the A group higher than it in the B group at 2、3、4 weeks,showing a significant difference(p<0.01)
Conclusion: Intermittent low-dose administration of rhPTH(1-34) can obviously promote the fracture healing,accelerat the differentiation of osteoblasts、the mineralization of bone and expression of BMP-2.
引文
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3. Reddi AH .Role of morphogenetic proteins in skeleted tissue engineering and regeneration [J].Natare Biotechnology,1998,16:247
4. Cook SD,Baffes GL,Wolfe MW,et al,Recombinant human bone morphogenetic protein-7moluces healing in a camine long-bone segmental mode[J].Clin Orthop,1994,301:302~312
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6. Klaushofer,Petorlik M.Pathophysiology of fracture healing.Radiology,1994,34(12):709
7. Bourque WT,Hall BK,Gross M.The presence of several growth factors during the stages of fracture repair[J].J Bone Joint Surg(Br),1993,75:282~287
8. Mc Donald BR,Gonen M,Cytokines and bone[J].Br Rheumat[J].1992,31:149~160
9. Harrs SE,Bonewald LF,Harrs MA et al.Effects of transforming growth factor-beta on bone nodule formation and expression of morphogenetic protion 2,osteopontin,alkaline phosphatase,and type collagen mRNA in longterm culture of fetal rat calvarial osteoblast[J].J Bone Miner Res,1994,9(8):855
10. Rubin MR,Cosman F,Lindsay R,et al.The anabolic effects of parathyroid hormone[J].Osteoporos Int,2002,13:267~277
11. Zhang KQ,Chen JW,Li QN,et al.Effect of intermittent injection of recombinant human parathyroid hormone on bone histomorphometry of ovariectomized rats.Acta Pharmacol Sin,2002,23(7):659~662
12. Neer RM,Arnaud CD,Zanchetta JR,et al.Effect of parathyroid hormone(1-34) on fractures and bone mineral density in postmenopausal women withosteoporosis[J].N Engl J Med,2001,344:1434~1441
13. Hock J M,Krishnan V, Onyia J E, Bidwell J P, Milas J,Stanislaus D.Osteoblast apoptosis and bone turnover[J].J Bone Miner Res, 2001,16(2):975-84.
14. Krieger I,Odrowaz-syoniewska G O steop tegerin[J].Ortop TraumaaRehabil,2004,6(1):123~129
15. Suda T,Takahashi N,Udagawa N,et al.Modulation of osteoclast differentiation and function by the new members of the tumor neciosis factor receptor and ligand families[J].Endocrine Rev,1999,20(3):345~357
16. Sasaki N,Kusano E.Bone and bone related biochemical examinations bone and collagen related metabolities,Measurement and clinical role OPG[J].Clin Calcium,2006,16(16):956~962
17. Lacey DL,Timms E,Tan H-L,et al.OPG ligand is a cytokine that regulates osteoclast differentiation and activation[J].Cell,1998,93:165~176
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