异种脱蛋白骨复合IGF-1修复兔股骨头坏死的实验研究
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摘要
目的：研究牛脱蛋白骨复合胰岛素样生长因子-1(IGF-1)对股骨头坏死的修复作用及相关问题,探讨其临床应用的可行性。方法：将60只新西兰大白兔(雌雄不限)随机分成三组,即IGF-1复合DPB组(简称IGF-1/DPB组)、单纯DPB组、空白对照组,其中空白组24只,其余组18只,三组再按术后观察时间进一步分为2周、4周、8周组。取900ngIGF-1溶于15ml的无菌蒸馏水中,投入18粒骨粒,经超声波振荡使液体完全浸入牛DPB骨粒并排出气泡；放置48h使溶液取代DPB孔隙中的空气,粗测每块吸附约50ng。自然干燥,得到复合人工骨,环氧乙烷熏蒸消毒。手术均取动物左髋关节,暴露髋关节囊及股骨颈后方,切开关节囊,以3.5mm钻头从股骨头颈交界处钻孔,钻入后向股骨头方向继续钻入,达到一定深度后以小刮匙刮除股骨头内50%松质骨,以浸足95%酒精小纱布块塞入骨隧道内持续30分钟。分别植入IGF-1/DPB、单纯DPB、空白对照。术后放回笼中饲养,自然活动。空白对照组随机取6只于3天后处死,取空洞周围股骨头组织做病理学检查；其余术后2周、4周、8周分批处死动物(每组每次处死6只)。处死家兔后拍摄股骨正位X线片,大体观察骨缺损区骨质生长情况,并取缺损区骨组织,沿股骨颈纵轴连续切片后进行HE染色。X线检查结果根据Lane骨移植X线片评分标准和应用X线骨密度仪进行分析,并将HE染色组织切片进行成骨细胞和破骨细胞的计数分析并观察血管生成及新生骨情况。根据上述观察指标来了解股骨头骨缺损区修复情况,综合评价IGF-1/DPB复合骨对股骨头坏死骨缺损的修复能力。结果：(1)X线骨密度仪分析：术后2周IGF-1/DPB组与DPB组骨密度无显著差别(P>0.05),术后4周,8周时IGF-1/DPB组骨密度较对照组高(P<0.05)；(2)Lane骨移植X线片评分：术后2周时IGF-1/DPB与DPB组无明显差别(P>0.05),4周、8周IGF-1/DPB组明显高于DPB组(P<0.05)；(3)组织学观察：空白组术后三天缺损区周围的骨小梁坏死,紊乱,出现碎片；骨细胞核固缩,溶解,骨陷窝空虚,证明酒精灭活股骨头坏死模型成立；4周时IGF-1/DPB组成骨细胞计数明显高于DPB组,统计学有显著性差异(P<0.05),骨陷窝形成,内有成熟骨细胞,毛细血管增生较明显；8周时IGF-1/DPB组移植材料被骨组织所取代,骨髓腔形成,DPB组骨样组织的成熟度不均一,大部分为编织骨,两组成骨细胞计数无显著性差异(P>0.05)。结论：DPB是IGF-1的理想载体,IGF-1/DPB复合骨在治疗股骨头坏死方面具备一定的潜能和优势,其成骨速度和质量明显优于单纯DPB,本研究所建立的缺损模型在评价生长因子治疗股骨头坏死的疗效方面具有可行性。
2
Objective:A new bone graft material was constructed by combining insulin -like growth factor (IGF-1)with deproteinized bovine cancellous bone (DPB).The ANFH rabbit model was developed that mimics the clinical situation with trapdoor bone-grafting,in order to evaluate the feasibility to use this method to repair avascular necrosis of femoral head (ANFH) in clinic。Methods:The model of ANFH was developed in the left femoral head in 54 rabbits, of which 18 defects were implanted with IGF-1/DPB composites,18 implanted with DPB,18 implanted nothing. Dissolve IGF-1 (900ng) in aseptic distillate (15ml),then put 18 DPBs into it, the mixed powder in 4 degree centigrade refrigerator. After exposing hip joint, drill hole between femoral head and neck with 3.5mm aiguille. Get rid of 50% cancellus bone of femoral head with little curette. Put a piece of gauze which dipped in 95% alcohol into the hole and keep 30min. then plant the IGF-1/DPB and DPB into the bone defects of ANFH respectively. The specimens were harvested respectively at the end of 2 week,4 week and 8 week after operation. In order to observe the formation of new bone and the degradation process of the materials, a series of examinations were carried out including of radiograph,histomorphology, bone density.The results of IGF-1/DPB group,DPB group and control group were compared on the same condition. result:Two week after operation, there is no statistical difference between the IGF-1/DPB group and the DPB group from radiological bone density and Lane-score examination(P> 0.05), but from tissue histology of HE osteoblast-score examination, there is obviously different between the two groups(P<0.05);At 4,8 week after operation, the rate and quality of new bone formation was statistical different between the IGF-1/DPB group and the DPB group from radiological bone density and Lane-score examination(P<0.05), and there is obviously difference in tissue histology of HE osteoblast-score examination also(P<0.05).Conclusion:DPB is an ideal carrier of IGF-1.The IGF-1/DPB composite has great potential in ANFH repairing. New bone formation is better than DPB group. The speed of degradation of IGF-1/DPB was evidently higher than DPB. The animal model in the current study is a useful tool for the evaluation of methods to treat osteonecrosis of femoral head. insulin-like growth factor-1 has the potential effect in treating avascular necrosis of femoral head.
2
Objective:A new bone graft material was constructed by combining insulin -like growth factor (IGF-1)with deproteinized bovine cancellous bone (DPB).The ANFH rabbit model was developed that mimics the clinical situation with trapdoor bone-grafting,in order to evaluate the feasibility to use this method to repair avascular necrosis of femoral head (ANFH) in clinic。Methods:The model of ANFH was developed in the left femoral head in 54 rabbits, of which 18 defects were implanted with IGF-1/DPB composites,18 implanted with DPB,18 implanted nothing. Dissolve IGF-1 (900ng) in aseptic distillate (15ml),then put 18 DPBs into it, the mixed powder in 4 degree centigrade refrigerator. After exposing hip joint, drill hole between femoral head and neck with 3.5mm aiguille. Get rid of 50% cancellus bone of femoral head with little curette. Put a piece of gauze which dipped in 95% alcohol into the hole and keep 30min. then plant the IGF-1/DPB and DPB into the bone defects of ANFH respectively. The specimens were harvested respectively at the end of 2 week,4 week and 8 week after operation. In order to observe the formation of new bone and the degradation process of the materials, a series of examinations were carried out including of radiograph,histomorphology, bone density.The results of IGF-1/DPB group,DPB group and control group were compared on the same condition. result:Two week after operation, there is no statistical difference between the IGF-1/DPB group and the DPB group from radiological bone density and Lane-score examination(P> 0.05), but from tissue histology of HE osteoblast-score examination, there is obviously different between the two groups(P<0.05);At 4,8 week after operation, the rate and quality of new bone formation was statistical different between the IGF-1/DPB group and the DPB group from radiological bone density and Lane-score examination(P<0.05), and there is obviously difference in tissue histology of HE osteoblast-score examination also(P<0.05).Conclusion:DPB is an ideal carrier of IGF-1.The IGF-1/DPB composite has great potential in ANFH repairing. New bone formation is better than DPB group. The speed of degradation of IGF-1/DPB was evidently higher than DPB. The animal model in the current study is a useful tool for the evaluation of methods to treat osteonecrosis of femoral head. insulin-like growth factor-1 has the potential effect in treating avascular necrosis of femoral head.
引文
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