高压氧促进激素性股骨头坏死多孔假体植入后骨整合的实验研究
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摘要
缺血性股骨头坏死晚期的治疗具有挑战性,因为它最常发生于年轻的、活动量大的患者。对于年轻人而言,这种疾病通常和类固醇的使用有关。当激素性股骨头坏死发展到Ficat III期和IV期时,全髋关节置换是唯一确实有效的治疗方法。但是激素性股骨头患者的骨骼质量较差,进行多孔表面股骨柄置换后界面骨整合情况令人担忧,尤其是年轻的、活动量大的患者更是如此。目前股骨头坏死多孔假体植入后骨整合的研究成为热点。
     高压氧(Hyperbaric Oxygen, HBO)在临床的应用越来越广泛,由于有促进水肿消退、抗菌、促进钙离子吸收等作用,它也广泛应用于骨科各领域的辅助治疗,如促进骨折愈合等。其促进多孔假体界面骨整合的研究多见于口腔科植入体的研究。HBO治疗能否改善激素性股骨头坏死患者股骨近端的骨质状况、能否促进多孔假体的骨整合还不是很清楚,目前国内外也缺乏这方面的文献报道。本实验通过三部分动物试验来初步解答这一问题。
     实验目的
     1.通过大鼠激素性股骨头坏死模型的建立,研究地塞米松对股骨近端组织学、BMP-2及其受体、细胞凋亡的影响,探讨不同剂量激素的使用与股骨近端骨质状况之间的关系。
     2.对激素性股骨头坏死的大鼠模型进行不同疗程高压氧的治疗,探讨高压氧对激素性股骨头坏死患者股骨近端组织学、BMP-2及其受体表达和细胞凋亡的影响,为高压氧用于促进骨整合提供理论基础。
     3.通过对兔激素性股骨头坏死模型进行高压氧治疗来探讨高压氧对多孔假体植入后骨结合率、新骨形成率、抗剪切强度的影响,为高压氧在临床上用于关节置换后的辅助治疗打下实验基础。
     技术路线
     1.将96只5月龄雄性Wister大鼠随机分为4组,对照组(C组)每周2次肌注生理盐水0.2ml/次、其余各组每次分别肌注地塞米松5mg/kg(L组)、10mg/kg(M组)、15mg/kg(H组),每周各2次。各组分别于用药后2、4、6、8周将大鼠分批处死,对股骨上1/3骨质进行组织切片HE染色观察骨小梁及骨皮质的变化、空骨陷窝率、免疫组化法观察BMP-2的表达情况、BMP-RⅠ的ELISA检测以及TUNEL法细胞凋亡检测。
     2.将90只4月龄雄性Wister大鼠进行大剂量地塞米松肌肉注射6周后,随机分为3组:对照组(A组)、一疗程组(B组)、三疗程组(C组)。以B、C组高压氧治疗开始后4、8、12周为观察的时间点,对三组大鼠股骨近端(股骨颈干内侧皮质交界水平至小转子下缘水平)骨质进行组织学观察、BMP-2和BMP-RⅠ表达的检测、BMP-RⅠ的ELISA检测以及TUNEL法细胞凋亡检测。
     3.将32只4月龄新西兰白兔肌注大剂量地塞米松共8周,造成股骨头坏死后随机分为对照组(C)、单纯高压氧组(H)、单纯rhBMP-2组(B)和高压氧加rhBMP-2组(U),每组8只动物。C、H组双侧股骨近端植入多孔假体,U、B组双侧股骨近端植入胶原蛋白复合rhBMP-2多孔假体。C、B组不予特殊处理,H、U组每天给予高压氧治疗30分钟,共20天。各组于术后4、8周、12周拍摄骨盆正位片。于术后12周处死所有动物,处死前7天和3天均肌注盐酸四环素(30mg/kg)行荧光标记。取右侧股骨标本用于硬组织切片,左侧标本用于生物力学顶出测试,检测抗剪切强度。
     研究结果
     1.组织学观察:实验组骨小梁/髓腔面积比、皮质/髓腔面积比随着用药时间的增加以及剂量的增加而降低,均低于对照组,空骨陷窝率则由随着用药剂量及时间的增加而增加的趋势。实验组的各时间点之间的差异具有统计学意义(p<0.05)。BMP-RⅠ的含量、股骨血管计数:随着用药剂量及用药时间的增加而进行性下降。BMP-2的相对含量随着用药量的增加而降低;各时间点间可以观察到一个趋势,即用药早期BMP-2有增高的趋势,而后期则有降低的趋势,用药量越大升高趋势越不明显而降低趋势越明显,反之升高趋势相对明显而降低趋势减弱。凋亡细胞计数:随着药量及用药时间的增加凋亡细胞数增加。
     2.三组骨小梁/髓腔面积比、皮质/髓腔面积比、BMP-2平均染色面积百分比、BMP-2染色的平均光密度、BMP-RⅠ的含量在各时间点的关系为:C组>B组>A组;A组的上述指标随时间呈降低的趋势,但是三个时间点间的差异无统计学意义(p>0.05),而B、C组上述5个指标则呈升高趋势。空骨陷窝率(ER)三组间的差异具有统计学意义(p<0.01);A组的ER有随时间增高的趋势;而B、C组ER随时间呈降低趋势,4周与8周、4周与12周间的差异具有统计学意义(p<0.01),而8周与12周间的差异不具有统计学意义(p>0.05)。
     3.组织学检测发现C组和B组植入体表面新生骨较少,呈突状伸向植入体表面,植入体孔隙中无新生骨;而H组植入体表面新生骨明显多于C组和B组,植入体表面多被新生骨覆盖,植入体孔隙内有大量新生骨形成;U组植入体表面完全被新生骨覆盖,但是植入体孔隙内新生骨明显比H组少。荧光显微镜检测发现C组仅在植入体周围及植入体孔隙中有少数区域存在荧光带,孔隙中的荧光带沿金属珠周围分布,荧光较暗淡;B组在植入体周围荧光带情况与C组类似,但是植入体孔隙中无荧光带分布,呈现出满视野黑暗区;H组无论植入体周围还是孔隙中多被明亮的荧光带包围、填充;U组植入体周围被明亮的荧光带包围,无暗淡区域,尽管植入体的孔隙多被荧光带填充,但是荧光带明显比H组暗淡。推出试验结果表明H组和U组的抗剪切强度明显高于C组和B组,四组间的差异具有统计学意义(p<0.05),U组略高于H组,差异不具有统计学意义(p>0.05),B组高于C组,差异具有统计学意义(p<0.05)。
     结论
     1.大剂量地塞米松可以降低股骨近端内BMP-RⅠ的含量及血管数量,促进细胞程序性凋亡及细胞坏死,大剂量地塞米松还可以降低BMP-2的表达,最终降低骨小梁密度及骨皮质厚度。用药量越大、时间越长,对股骨近端的影响越严重。
     2.停止使用大剂量激素后股骨近端的病理改变继续存在并在早期有加重的趋势,高压氧可以阻止甚至逆转这些病理改变;三疗程高压氧治疗效果优于一疗程。
     3.多孔假体植入后早期进行HBO治疗可以提高假体与骨的结合率,促进骨组织长入多孔假体中,增强假体-骨结合强度;HBO与rhBMP-2有协同作用,但rhBMP-2载体妨碍骨长入。
The treatment of avascular necrosis of femoral head is challenging, because it often occurs in young, active patients. For young people, avascular necrosis of femoral head is often associated with steroid. When femoral head necrosis induced by steroid developed to Ficat III and IV stage, total hip arthroplasty may be the most effective treatment. While the bone quality of patients taking steroid is poor, especially in those young, active patients. Now, integration of bone and porous implant come into a focus of research.
     Hyperbaric Oxygen used in clinic become more wide, for example, it can promote the healing course. If it can be used to promote the integration of bone and porous implant is steal unknown.
     Objective
     1. To evaluate the effects of different dosages of dexamethasone on proximal femurs in a rat model by histology, expression of BMP-2 and its receptor, apoptosis.
     2. To evaluate the effects of different courses of hyperbaric oxygen (HBO) therapy on proximal femur after short period of high dosage of glucocorticoid application in rat model by assessing histology, expression of BMP-2 and its receptor.
     3. To disgust the early effect of HBO therapy on bone ingrowth in porous implant in a rabbit model of avascular necrosis of femoral head induced by dexamethasone.
     Methods:
     1. Ninety-six male rats of 5-month old were divided into 4 groups: control group (Group C), 5mg/kg group (Group L), 10mg/kg (Group M), 15mg/kg (Group H), drugs were administered twice a week by intramuscular injection. Observe the changes of histology, expression of BMP-2 and its receptor and apoptosis of proximal femurs.
     2. Ninety 4-month-old Wister male rats were administered high dosage of dexamethasone for 6 weeks, and then they were divided into 3 groups: Control Group (Group A), One-course Group (Group B), Three -course Group (Group C). At time of 4, 8, 12 weeks after treatment of HBO therapy, histology, expression of BMP-2 and its receptor (BMP-RⅠ) of the upper 1/3 of femur were assessed respectively.
     3. Thirty-two 4 month old New Zealand rabbit were injected with dexamethason intramuscularly for 8 weeks. After the model of necrosis of femoral head established, they were divided into 4 groups randomly, they were control group (Group C), HBO group (Group H), rhBMP-2 group (Group B) and HBO plus rhBMP-2 or union group (Group U), each goup had 8 rabbits. The femurs of rabbits in Group C and H were implanted with bare porous implants; while the femurs of rabbits in Group U and B were implanted with implants compounded with rhBMP-2. Group C and B were under no any interference; Group H and U were treated 30 minutes with HBO each day for 20 days. All groups gain roentgenology films at 4, 8 and 12 weeks postoperative. All rabbits were killed at 12 weeks, in 7 days and 3 days before they were killed, they were injected with tetracycline intramuscularly. All samples of right femurs were used for hard tissue slices, while all samples of left femurs were used for biomechanics test.
     Results
     1. Area ratio of bone trabeculae and medullary cavity, area ratio of cortical bone and medullary cavity, contents of BMP-RⅠreduced with time and increased dosages in experimental groups, all of them are lower than that of Group C. The number of empty bone lacunae and the number of apoptosis cells have a trend of increasing with time and increased dosages. Average percentage of dyed areas and average optical density of BMP-2 in Group L are markedly higher than that of Group C at 2 weeks and then decreased, by the 8th week they are significantly lower than that of Group C. While Average percentage of dyed areas and average optical density of BMP-2 in Group M and H are at approximately the normal level at 2 weeks. They decreased gradually at 4, 6 and 8 weeks to a lower level.
     2. The vessel numbers of cavity in Group C and D are larger than that of Group A and bone trabeculae and cortical bone of Group C and D are thicker than those of Group A. The relations of three groups with regard to area ratio of bone trabeculae and medullary cavity (TCR), area ratio of cortical bone and medullary cavity (CCR), average percentage of dyed areas (DAP) and average optical density (OD) of BMP-2 and contents of BMP-RⅠ(BRC) of proximal femurs are Group C> Group B> Group A, differences are significant (p<0.01). TCR, CCR, DAP, OD, BRC in Group A show a trend of decreasing, while there are no significant differences between 3 phases (p>0.05). TCR, CCR, DAP, OD, BRC in Group B and C show trends of increasing, there are significant differences on the contents of BMP-RⅠbetween 3 phases (p<0.01); there are significant differences between 4- and 8-week and 4- and 12-week about the rest indexes (p<0.01), while there is no significant difference between 8- and 12-week (p>0.05). As to the empty rate of bone lacunae (ER), there is significant difference between three Groups (p<0.01). The ER in Group A has a trend of increasing with time, however, there is no significant difference between phases (p>0.05); the ER in Group B and C have trends of decreasing, there are significant differences between 4- and 8-week and 4- and 12-week (p<0.01 both), while there is no significant difference between 8- and 12-week (p>0.05).
     3. In histology, we find that the situation of new bone formation and contact of bone and implants in Group C and B are similar, there is few new bone on the surface of implants and there is no new bone within porous implants. The new bone on the surface of implants in Group H is greater than that in Group C and B, and there is much new bone formation within porous implants in Group H. The surface of implants in Group U is all covered by new bone, but new bone in porous implants is fewer than that of Group H. The outcome of fluorescence test is that there is few fluorescence areas around and within porous implants, and fluorescence band is dim. The fluorescence band around implants in Group B is similar to that of group C, while there is no fluorescence band in porous implants, there are all dark areas within implants under scope. All spaces around and within implants are filled with bright fluorescence band. Spaces around implants in Group U are also filled with bright fluorescence band, however, though porous spaces are filled with fluorescence band , it’s dimmer than that of Group H. The result of pull out test show that anti- shearing force in Group H and U is greater than that in Group C and B, the differences are significant (p<0.05). Anti- shearing force in Group U is little greater than that in Group H, there is no difference between the two groups (P>0.05). Anti- shearing force in Group B is greater than that in Group C, the difference is significant (p<0.05).
     Conclusions
     1. High dosages of dexamethasone can damage the quality of proximal femur; the higher the dosages of dexamethasone are administered and the longer the administering time lasts, the poorer of the proximal femur will be.
     2. After administered glucocorticoid for a short term, pathological changes are still maintained and have trends of increasing in early stage. HBO can reverse these changes. The outcome of 3-course HBO therapy is better than that of 1-course therapy.
     3. HBO therapy can improve integration rate of bone and implant, promote new bone ingrowth into porous implant, enhance the integration strength of bone and implant. HBO and rhBMOP-2 have cooperative effect, but the carrier of rhBMP-2 can prevent bone ingrowth into implant.
引文
1. Weinstein RS, Manolagas SC. Apoptosis in glucocorticoid-induced bone disease. Curr Opin Endocrinol Diabetes 2005;12:219-23.
    2.魏青,杨杏芬,刘力,等。激素性股骨头坏死动物模型的建立和评价。中国骨质疏松杂志1999;5:26-8.
    3. Bauer TW, Muschler GF. Bone graft materials. An overview of basic science. Clin Orthop 2000;371:10-27.
    4. Reddi AH. Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop 1998;355(Suppl):S66-S72.
    5. Reddi AH. Bone morphogenetic proteins: from basic science to clinical applications. J Bone Joint Surg Am 2001;1:S1–S6.
    6. Pietrzak WS, Woodell-May J, McDonald N. Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone matrix. J Craniofac Surg 2006; 17: 84-90.
    7. Bouxsein MI, Tourek T, Blake CA, et al. RhBMP-2 accelerates healing in a rabbit ulnar osteotomy model. J Bone Joint Surg 2001;83A:1219-30.
    8. Boyne PJ. Animal studies of application of rhBMP-2 in maxillofacial reconstruction. Bone 1996;19 (Suppl):83S-92S.
    9. Boyne PJ, Marx RE, Nevins M, et al: A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. Int J Periodontics Restorative Dent 1997;17:11-25.
    10. Sciadini MF, Johnson KD. Evaluation of rhBMP-2 as a bone-graft substitute in a canine segmental defect model. J Orthop Res 2000;18:289-302.
    11. Welch RD, Jones AL, Bucholz RW, et al. Effect of rhBMP-2 on fracture healing in a goat tibial fracture model. J Bone Miner Res 1998;13:1483-90.
    12. Teichert-Kuliszewska K, Kutryk MJ, Kuliszewski MA, et al. Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension. Circul Res 2006;3: 209-17.
    13. Miyazono K. Signal transduction by bone morphogenetic protein receptors: Functional roles of Smad proteins. Bone 1999;25:91-3.
    14. Wang EA, Rosen V, D’Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 1990;87:2220-4.
    15. Wozney JM, Rosen V. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop 1998;346:26-37.
    16. Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 2002;395:110-20.
    17. Sandhu HS, Toth JM, Diwan AD, et al. Histologic evaluation of the efficacy of rhbmp-2 compared with autograft bone in sheep spinal anterior interbody fusion. Spine 2002;27:567-75.
    18.何爱珊,廖威明,李佛保,等。HA梯度涂层复合BMP人工股骨柄的研究。中华骨科杂志2005;25:400-3.
    19.牟明威,张新,徐莘香,等。假体四种表面处理的体内植入实验。中华骨科杂志2004;24:179-83.
    20. Weinstein RS, Nicholas RW. Apoptosis of osteocytes in glucocorticoid induced osteonecrosis of the hip. J Clin Endocrinol Metab 2000;85:2907-12.
    1. Boss H, Misselevich I. Osteonecrosis of the femal head of laboratory animals the lessons learned from a comparative study of osteonecrosis in man and experimental animals. Vet Pathol 2003;40:345-54.
    2. Ivankovich DA, Rosenberg AG, Malamis A. Reconstructive Options for Osteonecrosis of the Femoral Head. Tech Othop 2001;16:66-79.
    3. Tanzer M, Karabasz D, Krygier JJ, et al. Bone augmentation around and within porous implants by local bisphosphonate elution. Clin Orthop Relat Res 2005;441:30-9.
    4. Wang IC, Ueng WN, Yuan LJ, et al. Early administration of hyperbaric oxygen therapy in distraction osteogenesis: a quantitative study in new zealand rabbits. J Trauma 2005;58: 1230-5.
    5. Mutschler W, Muth CM. Hyperbaric oxygen therapy in trauma surgery. Unfallchirurg 2001;104:101-2.
    6. Coulson DB, Ferguson AB Jr., Diehl RC. Effect of hyperbaric oxygen on the healing femur of the rat. Surg Forum 1996;17: 449-50.
    7. Haapaniemi T, Nylander G, Kanje M, et al. Hyperbaric oxygen treatment enhances regeneration of the rat sciatic nerve. Exp Neurol, 1998;149:433-8.
    8. Bragdon CR, Doherty AM, Rubash HE, et al. The John Charnley award: the efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model. Clin Orthop Relat Res 2003;417: 50-61.
    9. Ono I, Tateshita T, Inoue M, et al. In vivo strength enhancement of hydroxyapatite combined with rhBMP-2. J Bone Miner Metab, 1998; 16: 81-7.
    10. Stenport VF, Johanson C, Heo SJ, et al. Titanium implants and BMP-7 in bone: an experimental model in rabbits. J Mater Sci 2003,14:247-54.
    11. Weinstein RS. The pathogenesis of glucocorticoid-induced osteoporosis. Clin ExpRheumatol 2000; 18(Suppl 21):S35-S40.
    12. Weinstein RS. Glucocorticoid-induced osteoporosis. Rev Endocr Metab Disord 2001;2:65-73.
    13. Manolagas SC, Weinstein RS. Perspective: new developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res 1999;14:1061-6.
    14. Lafage-Proust MH, Boudignon B, Thomas T. Glucocorticoid-induced osteoporosis: pathophysiological data and recent treatments. Joint Bone Spine 2003;70:109-18.
    15. Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoidinduced osteoporosis. Bone 2004;34:593-8.
    16. Weinstein RS, Manolagas SC. Apoptosis in glucocorticoid-induced bone disease. Curr Opin Endocrinol Diabetes 2005;12:219-23.
    17. Jensen WK, Anderson PA, Nel L, et al. Bone ingrowth in retrieved bryan cervicaldisc prostheses. Spine 2005;30:2497-502.
    18. Coulson DB, Ferguson AB Jr., Diehl RC. Effect of hyperbaric oxygen on the healing femur of the rat. Surg Forum 1996;17: 449-50.
    19. Miyazono K. Signal transduction by bone morphogenetic protein receptors: Functional roles of Smad proteins. Bone 1999;25:91-3.
    20. Wang EA, Rosen V, D’Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 1990;87:2220-4.
    21. Wozney JM, Rosen V: Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop 1998;346:26-37.
    22. Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 2002;395:110-20.
    23.常巍,程少华,宋跃明。高压氧治疗兔激素性股骨头缺血坏死的病理学变化实验研究。中国矫形外科杂志2005,13:1323-5.
    24.黄振新。0.15MPa高压氧治疗骨折的疗效分析。现代临床医学生物工程学杂志2004;10:248-9.
    1. Ivankovich DA, Rosenberg AG, Malamis A. Reconstructive options for osteonecrosis of the femoral head. Tech Othop 2001;16:66-79.
    2.蒋立坚,陈光晔,陈伟良,等。高压氧影响游离植骨种植体骨整合的组织学研究。实用口腔医学杂志2000;16:285-6.
    3.徐小良,王坤正,吕荣。四环素荧光标记不脱钙骨甲酯包埋法。临床与实验病理学杂志2001;17:173.
    4. Engh CA, Massin P, Suthers KE. Roentgenography assessment of the biologic fixation of porous-surface demoral components. Clin Orthop 1990;257:107-28.
    5.牟明威,张新,徐莘香,等。假体四种表面处理的体内植入实验。中华骨科杂志2004;24:179-83.
    6. Tanzer M, Karabasz D, Krygier JJ, et al. Bone augmentation around and within porous implants by local bisphosphonate elution. Clin Orthop Relat Res, 2005;441:30-9.
    7. D’Antonio JA, Capello WN, Manley MT, et al. Hydroxyapatite femoral stems for total hip arthroplasty: 10- to 13-year followup. Clin Orthop Relat Res 2001;393:101-11.
    8. Engh CA, Claus AM, Hopper RH, Engh CA: Long-term results using the anatomic medullary locking prosthesis. Clin Orthop Relat Res 2001;393:137–46.
    9. Peter B, Pioletti DP, Laib S, et al. Calcium phosphate drug delivery system: Influence of local zoledronate release on bone implant osseointegration. Bone 2004;36:52–60.
    10. Sychterz CJ, Claus AM, Engh CA. What we have learned about long-term cementless fixation from autopsy retrievals. Clin Orthop Relat Res 2002;405:79–91.
    11. Teloken MA, Bissett G, Hozack WJ, Sharkey PF, Rothman RH: Ten to fifteen-yearfollow-up after total hip arthroplasty with a tapered cobalt-chromium femoral component (tri-lock) inserted without cement. J Bone Joint Surg 2002;84A:2140–4.
    12. Bobyn JD, Jacobs JJ, Tanzer M, et al. The susceptibility of smooth implant surfaces to peri-implant fibrosis and migration of polyethylene wear debris. Clin Orthop Relat Res 1995;311:21–39.
    13. Barrack RL, Cook SD, Salkeld SL, et al. Induction of bone ingrowth from an acetabular defect to a porous surface with osteogenic protein-1. Clin Orthop Relat Res 2003;417:41-9.
    14. Bragdon CR, Doherty AM, Rubash HE, et al. Efficacy of MBP-2 to induce bone ingrowth in gap and non-gap regions of a THR model. Clin Orthop Relat Res 2003;417:50–61.
    15. Cole BJ, Bostrom MPG, Pritchard TL, et al. Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat. Clin Orthop Relat Res 1997;345:219-28.
    16. Cook SD, Salkeld SL, Patron LP, et al. The effect of demineralized bone matrix gel on bone ingrowth and fixation of porous implants. J Arthroplasty 2002;17:402-8.
    17. Sumner DR, Turner TM, Purchio AF, et al. Enhancement of bone ingrowth by transforming growth factor beta. J Bone Joint Surg 1995; 77A:1135-47.
    18. Sumner DR, Turner TM, Urban RM, et al. Locally delivered rhTGF-2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury. J Orthop Res 2001;19:85-94.
    19. Sumner DR, Turner TM, Urban RM, et al. Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model. J Orthop Res 2004;22:58-65.
    20. Tanzer M, Harvey E, Kay A, et al. Effect of noninvasive low intensity ultrasound on bone growth into porouscoated implants. J Orthop Res 1996;14:901-6.
    21. Tanzer M, Kantor S, Bobyn JD. Enhancement of bone growth into porous intramedullary implants using non-invasive low intensity ultrasound. J Arthroplasty 2002;19:195-9.
    22. Jensen WK, Anderson PA, Nel L, et al. Bone ingrowth in retrieved bryan cervicaldisc prostheses. Spine 2005;30:2497-502.
    23. Takahata M, Kotani Y, Abumi K, et al. Bone ingrowth fixation of artificial intervertebral disc consisting of bioceramic-coated three-dimensional fabric. Spine 2003;28: 637-44.
    24. Glassman AH, Crowninshield RD, Schenck R, et al. A low stiffness composite biologically fixed prosthesis. Clin Orthop Relat Res 2001;393: 128-36.
    25. Engh CA, Hooten JP, Zettl-Shaffer KF, et al. Evaluation of bone ingrowth in proximally and extensively porous-coated anatomic medullary locking prostheses retrieved at autopsy. J Bone Joint Surg [Am] 1995;77:903–10.
    26. Bloebaum RD, Bachus KN, Jensen JW, et al. Porous-coated metal-backed patellar components in total knee replacement: A postmortem retrieval analysis. J Bone Joint Surg [Am] 1998;80:518–28.
    27. Harvey EJ, Bobyn JD, Tanzer M, et al. Effect of flexibility of the femoral stem on bone remodeling and fixation of the stem in a canine total hip arthroplasty model without cement. J Bone Joint Surg [Am] 1999;81:93–107.
    28. McAfee PC, Cunningham BW, Orbegoso CM, et al. Analysis of porous ingrowth in intervertebral disc prostheses, a nonhuman primate model. Spine 2003;28: 332–340.
    29. Kold S, Rahbek O, Vestermark M, et al. Bone compaction enhances fixation of weightbearing titanium implants. Clin Orthop Relat Res 2005;431:138-44.
    30. Bragdon CR, Burke D, Lowenstein JD, et al. Differences in stiffness of the interfacebetween a cementless porous implant and cancellous bone in vivo in dogs due to varying amounts of implant motion. J Arthroplasty 1996;11:945-51.
    31. Jasty M, Bragdon C, Burke D, et al. In vivo skeletal responses to porous-surfaced implants subjected to small induced motions. J Bone Joint Surg 1997;79A:707-14.
    32. Yee AJ, Kreder HK, Bookman I, et al. A randomized trial of hydroxyapatite coated prostheses in total hip arthroplasty. Clin Orthop Relat Res 1999;366:120-32.
    33. Gosain AK, Riordan PA, Song LS, et al. A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: partⅡ. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects. Plast Recons Surg 2004;114: 1155-63.
    34. Korovessis PG, Deligianni DD. Role of surface roughness of titanium versus hydroxyapatite on human bone marrow cells response. J Spinal Disorder Tech 2002;15:175-83.
    35. Tibbles PM, Edelsburg JS. Hyperbaric oxygen therapy. N Engl J Med 1996;334:1642-8.
    36. Gabb G, Robin ED. Hyperbaric oxygen– a therapy in search of diseases. Chest 1987;92:1074-82.
    37. Leach RM, Rees PJ, Whilmshurst P. Hyperbaric oxygen therapy. Br Med J 1998; 317:1140-3.
    38. Miyazono K. Signal transduction by bone morphogenetic protein receptors: Functional roles of Smad proteins. Bone 1999;25:91-3.
    39. Wozney JM, Rosen V. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop 1998;346:26-37.
    40. Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinanthuman bone morphogenetic protein-2. Clin Orthop Relat Res 2002;395:110-20.
    41. Bouxsein MI, Tourek T, Blake CA, et al. RhBMP-2 accelerates healing in a rabbit ulnar osteotomy model. J Bone Joint Surg 2001;83A:1219-30.
    42. Boyne PJ. Animal studies of application of rhBMP-2 in maxillofacial reconstruction. Bone 1996;19 (Suppl):83S-92S.
    43. Boyne PJ, Marx RE, Nevins M, et al. A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. Int J Periodontics Restorative Dent 1997;17:11-25.
    44. Sciadini MF, Johnson KD. Evaluation of rhBMP-2 as a bone-graft substitute in a canine segmental defect model. J Orthop Res 2000;18:289-302.
    45. Welch RD, Jones AL, Bucholz RW, et al. Effect of rhBMP-2 on fracture healing in a goat tibial fracture model. J Bone Miner Res 1998;13:1483-90.
    46.赵继军,杨述华,胡勇,等。高压氧对大剂量激素用药后股骨近端影响的早期实验研究。中华物理医学与康复杂志2007;
    47. Coulson DB, Ferguson AB Jr., Diehl RC. Effect of hyperbaric oxygen on the healing femur of the rat. Surg Forum. 1996;17: 449-50.
    48. Yablon IG, Cruess RL. The effect of hyperbaric oxygen on fracture healing in rats. J Trauma 1968;8:186-202.
    49. Wray JB, Rogers JS. Effect of hyperbaric oxygenation upon fracture healing in the rat. J Surg Res 1968;8:373-8.
    1. Hampson NB, ed. Hyperbaric Oxygen Therapy: 1999 Committee report. Kensington MD, Undersea and Hyperbaric Medical Society, 1999.
    2. Vrabec JT, Clements KS, Mader JT. Short-term tympanostomy in conjunction with hyperbaric oxygen therapy. Laryngoscope 1998; 108:1124-8.
    3. Tibbles PM, Edelsburg JS. Hyperbaric oxygen therapy. N Engl J Med 1996;334:1642-8.
    4. Gabb G, Robin ED. Hyperbaric oxygen– a therapy in search of diseases. Chest 1987;92:1074-82.
    5. Leach RM, Rees PJ, Whilmshurst P. Hyperbaric oxygen therapy. Br Med J 1998; 317:1140-3.
    6. Myers RAM. Hyperbaric oxygen therapy for trauma: crush injury, compartment syndrome, and other acute traumatic peripheral ischaemias. Int Anesthesiol Clin 2000;38:139-51.
    7. Zamboni WA, Roth AC, Russell RC, et al. Morphological analysis of the microcirculation during reperfusion of ischaemic skeletal muscle and the effect of hyperbaric oxygen. Plastic Reconstr Surg 1993;91:1110-23.
    8. Thom SR. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990;105:340-4.
    9. Villanucci S, Di Marzio GE, Scholl M, et al. Cardiovascular changes induced by hyperbaric oxygen therapy. Undersea Biomed Res 1990;17(suppl.1):117.
    10. Wattel F, Mathieu D, Neviere R, et al. Hyperbaric therapy: acute peripheral ischaemia and compartment syndrome: a role for hyperbaric oxygenation. Anaesthesia 1998;53(suppl.2):63-5.
    11. MutschlerW,MuthCM.Hyperbaricoxygentherapyintraumasurgery.Unfallchirurg,2001,104:101-102.
    12.徐旭光,张波,周永霞,等.高压氧促进骨再生的实验研究.中华理疗杂志,1989,12:97-98.
    13.张立国,宋映女,曹连生,等.高压氧对骨折愈合的临床观察.中华航海医学杂志,1997,4:116-117.
    14.林忠豪,张玲,练克俭,等.高压氧综合治疗肢体创伤疗效观察.中华理疗杂志,2000,23:147-149.
    15. Coulson DB, Ferguson AB Jr., Diehl RC. Effect of hyperbaric oxygen on the healing femur of the rat. Surg Forum 1996;17: 449–450.
    16. Wang IC, Ueng WN, Yuan LJ, et al. Early administration of hyperbaric oxygen therapy in distraction osteogenesis: a quantitative study in new zealand rabbits. The Journal of Trauma 2005, 58 (6): 1230-1235
    17.马瑞山.航空航天生理学.西安:陕西科学技术出版社,1999.142-143.
    18.朱源.高压氧治疗手外伤血液循环危象94例.中华航海医学杂志,1997,4:49-50.
    19.黄志强,李秀芬.高压氧治疗股骨头无菌坏死的疗效观察.中华航海医学杂志,1996,3:253.
    20.杨宝兴,邵印麟,朱晓蕾.高压氧结合活血壮骨汤治疗股骨头无菌坏死。中国厂矿医学,2001,14:63-64.
    21.蒋美英.高压氧对周围神经损伤后再生作用机理的探讨.中华航海医学杂志,1994,1:32-33.
    22.崔波,于大中,钱抚生,等.周围神经卡压松解的实验研究及临床应用.现代康复,1998,2:998-999.
    23. HaapaniemiT,NylanderG,KanjeM,etal.Hyperbarieoxygentreatmentenhancesregenerationoftheratsciaticnerve.ExpNeurol,1998,149:433-438.
    24.赵德伟,朱景斌,郭林.腓肠神经移植修复周围神经缺损116例.中华显微外科杂志,1996,19:270-272.
    25. VieraC,GalvezC,GarrascoB,etal.Astudyofperipheralneu-ralconduction,motorandsensory,indiabetiepatientstreatedwithhyperbaricoxygenation.RevNeurol,1999,28:868-872
    26.刘秋芹,易治,庄永青.高压氧在周围神经修复中的作用.广东医学,1997,18:300-301.
    27. DuckerTB.Spinalcordoxygenandbloodflowintrauma.JSurgForum,1971,22:413-414
    28. GelderdTB.Behavioralandlightmicroscopicevaluationofhy-perbaricoxygenanddimethylsulfoxidtreatmentsfollowingspinalcordtransactioninrats.AnatRec,1980,196:62-63.
    29. Fawceff JW, Keynes RJ. Peripheral nerve regeneration. Ann Rev Neuresci, 1990, 13: 43-45.
    30.余海,田润兰,潘小雯,等.高压氧治疗在神经修复与再生过程中的作用.现代康复,2001,5:(3):48-49.
    31.杜全印,王爱民,郭庆山,等.高压氧与带血供周围神经移植对成鼠损伤脊髓诱发电位的影响.中国矫形外科杂志,2001,8: 483-484.
    32.徐伟刚,徐和平,陶恒沂,等.脊髓损伤的高压氧治疗.中华航海医学与高气压医学杂志,2001,8:113-115.
    33.陈韬.高压氧治疗急性颈髓损伤.国外医学骨科学分册,2001,22:118-119.
    34. Hampson N, Atik D. Central nervous system oxygen toxicity during routine hyperbaric oxygen therapy. Undersea Hyperb Med 2003;30:147-53.
    35. Feldmeier JJ, Heimbach RD, Davolt DA, et al. Does hyperbaric oxygen have a cancer causing or promoting effect? A review of the pertinent literature. Undersea Hyperb Med 1994;21:467-75.
    36. Feldmeier J, Carl U, Hartmann K, et al. Hyperbaric oxygen: does it promote growth or recurrent of malignancy? Undersea Hyperb Med 2003;30:1-18.
    37. Sheffield PJ, Desautels DA. Hyperbaric and hypobaric fires: a 73 year analysis. Undersea Hyperb Med 1997;24:153-64.
    38.余平,牟燕华.高压氧治疗中的毒副作用及预防.临床荟萃,2001,16:71-72.

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