体外冲击波治疗家兔股骨头坏死的实验研究
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摘要
目的：观察并对比体外冲击波对物理损伤型和激素型兔股骨头坏死的疗效，证明冲击波是一条安全可靠、疗效较高的治疗股骨头缺血性坏死的途径，并阐述其作用机理，为临床应用提供证据。
方法：22只日本大耳白兔，随机分为物理损伤组(11只)和激素组(11只)，物理损伤组用手术加液氮冷冻造模，激素组用甲基强的松龙加马血清造模。每组左后腿作为对照组，不予治疗，右后腿作为治疗组，用冲击波治疗。分别于治疗后2、4、8周处死，取材，X线摄片，并作组织学和电子显微镜观察。计数股骨头软骨下骨的空骨陷窝率，成骨细胞数和血管计数，并进行统计分析。
结果：冲击波治疗后，第二周、第四周X线片示冷冻组左、右股骨头坏死面积大小无明显差异。第八周坏死面积大小差异明显，其中3只左侧股骨头完全塌陷，残留部很小，其余5只残留部面积也均小于正常股骨头的1／2。右侧股骨头塌陷程度较轻，圆形轮廓尚在，坏死面积均没有超过正常股骨头面积的1／2。激素组第二周、第四周X片示股骨头左右对比无明显差异，第八周，6只兔左侧股骨头面积比右侧小，2只差异不明显。光镜下两组兔左右侧股骨头病理切片10个中倍视野内计数骨陷窝、空骨陷窝，成骨细胞数和血管数，经统计分析，冷冻组和激素组治疗组空骨陷窝率显著低于对照组(P＜0.001)，成骨细胞计数和血管计数显著高于对照组(P＜0.01)。电镜观察治疗组比对照组成骨细胞成骨活跃。
结论:冲击波疗法治疗冷冻致股骨头坏死有较好疗效，对激素性股
骨头坏死疗效不如冷冻致股骨头坏死疗效显著，有待进行长期实验观
察。
Objective: To investigate and contrast the effect of physical damage and hormonal of rabbits' femoral head necrosis. To Study the therapeutic mechanism of medication and to look for a safe and reliable method for clinical treatment.
Methods: Twenty-two Japanese rabbits were used for establishing the model of femoral head necrosis .The animals were divided into two group at random, freezing group (11)which were operated and used liquid nitrogen to freezing the femoral head. Hormonal group(11) which were injected horse serum 5mg kg-1twice and Methylpredisolone 40 mg kg-1 three times .The left back legs of all rabbits did not treated as control group, the right back legs were treaded with extrocorporeal shock wave(ESW). X-ray, pathological examination and electron microscope examination were adopted to observe the changes of the femoral head in different periods(after therapy 2 , 4, 8weeks).
Results: After extrocorporeal shock wave treated, the size of femoral head necrosis area doesn't show a significant difference between the right and left legs by X-ray picture in the frozen group at the 2th and 4th week. However, the difference is obviously observed in the X-ray picture at the 8th week, three rabbits' left femoral head collapsed totally and there is few bone remained, the other five rabbits' remained size of the left side femoral head is smaller than half of normal femoral head. But the right femoral head of all animals are collapsed slightly, the size of collapse part is smaller than half of normal femoral head. Similarly, the shape of left femoral heads isn't different from the right femoral heads' at the 2th and 4th week. At the 8th week after extrocorporeal shock wave treated, the size of six rabbits' left side femoral heads is smaller than right side femoral heads, two rabbits' size of left side femoral head haven't difference contrast with the rights'. We count the number of lacuna, empty lacuna, osteoblast and blood vessel in ten view of microscope by 100 times magnification, calculated the statistical date and conclude the treated group' s ratio of empty lacuna is less than the control group' s notably(P<0.001), the number of osteoblast (P<0.01) and blood vessel (P<0.05) are more than the control group notably.
Conclusion: Extrocorporeal shock wave is a good method to treat the freezing femoral head necrosis. Its effect isn't obviously to the hormonal femoral head necrosis in 8 weeks. The mechanism may consist in re-passing the blocked vessel by calving the thrombus and promoting osteoblast developing.
方法：22只日本大耳白兔，随机分为物理损伤组(11只)和激素组(11只)，物理损伤组用手术加液氮冷冻造模，激素组用甲基强的松龙加马血清造模。每组左后腿作为对照组，不予治疗，右后腿作为治疗组，用冲击波治疗。分别于治疗后2、4、8周处死，取材，X线摄片，并作组织学和电子显微镜观察。计数股骨头软骨下骨的空骨陷窝率，成骨细胞数和血管计数，并进行统计分析。
结果：冲击波治疗后，第二周、第四周X线片示冷冻组左、右股骨头坏死面积大小无明显差异。第八周坏死面积大小差异明显，其中3只左侧股骨头完全塌陷，残留部很小，其余5只残留部面积也均小于正常股骨头的1／2。右侧股骨头塌陷程度较轻，圆形轮廓尚在，坏死面积均没有超过正常股骨头面积的1／2。激素组第二周、第四周X片示股骨头左右对比无明显差异，第八周，6只兔左侧股骨头面积比右侧小，2只差异不明显。光镜下两组兔左右侧股骨头病理切片10个中倍视野内计数骨陷窝、空骨陷窝，成骨细胞数和血管数，经统计分析，冷冻组和激素组治疗组空骨陷窝率显著低于对照组(P＜0.001)，成骨细胞计数和血管计数显著高于对照组(P＜0.01)。电镜观察治疗组比对照组成骨细胞成骨活跃。
结论:冲击波疗法治疗冷冻致股骨头坏死有较好疗效，对激素性股
骨头坏死疗效不如冷冻致股骨头坏死疗效显著，有待进行长期实验观
察。
Objective: To investigate and contrast the effect of physical damage and hormonal of rabbits' femoral head necrosis. To Study the therapeutic mechanism of medication and to look for a safe and reliable method for clinical treatment.
Methods: Twenty-two Japanese rabbits were used for establishing the model of femoral head necrosis .The animals were divided into two group at random, freezing group (11)which were operated and used liquid nitrogen to freezing the femoral head. Hormonal group(11) which were injected horse serum 5mg kg-1twice and Methylpredisolone 40 mg kg-1 three times .The left back legs of all rabbits did not treated as control group, the right back legs were treaded with extrocorporeal shock wave(ESW). X-ray, pathological examination and electron microscope examination were adopted to observe the changes of the femoral head in different periods(after therapy 2 , 4, 8weeks).
Results: After extrocorporeal shock wave treated, the size of femoral head necrosis area doesn't show a significant difference between the right and left legs by X-ray picture in the frozen group at the 2th and 4th week. However, the difference is obviously observed in the X-ray picture at the 8th week, three rabbits' left femoral head collapsed totally and there is few bone remained, the other five rabbits' remained size of the left side femoral head is smaller than half of normal femoral head. But the right femoral head of all animals are collapsed slightly, the size of collapse part is smaller than half of normal femoral head. Similarly, the shape of left femoral heads isn't different from the right femoral heads' at the 2th and 4th week. At the 8th week after extrocorporeal shock wave treated, the size of six rabbits' left side femoral heads is smaller than right side femoral heads, two rabbits' size of left side femoral head haven't difference contrast with the rights'. We count the number of lacuna, empty lacuna, osteoblast and blood vessel in ten view of microscope by 100 times magnification, calculated the statistical date and conclude the treated group' s ratio of empty lacuna is less than the control group' s notably(P<0.001), the number of osteoblast (P<0.01) and blood vessel (P<0.05) are more than the control group notably.
Conclusion: Extrocorporeal shock wave is a good method to treat the freezing femoral head necrosis. Its effect isn't obviously to the hormonal femoral head necrosis in 8 weeks. The mechanism may consist in re-passing the blocked vessel by calving the thrombus and promoting osteoblast developing.
引文
1. Brunner W Thuringer R, Ascher G, et al. Die extrakorporelle stobwellentherapie in der orthopadie-Drei-monats-ergebnisse in 443 fallen. Orthop. Prax. 1997, 33:461～464.
2. Haist J, von Keitz-steeger D, Mohr G, et al. The Orthopaedic Shock wave Therary in the treatment of chronic insertion Tendopathy and Tendinosis Calcarea. In Siebert W, Buch M (eds). Extracorporeal Shock Waves in Orthopaedics. Berlin, Sprnger Verlag. 1997, 159～163.
3. Chaussy C, Eisenberge F, Jocham D, et al (eds). High Energy Shock Wave in medicine. Stuttgart, Thieme. 1997. 235～238.
4. Coombs R, Schaden W, Zhou SSH: Musculoskeletal Shoc Wave Therary. London, Greenwich Medical Media. 2000. 146～152.
5. Haupt A, Haupt G, Ekkernkamp A, et al. Influence of shock waves on fracture healing. Urologe. 1992,31: 43～46.
6. Johannes E J, Kaulesar-Sukul DM, Metura E, et al. High energy shock waves for the treatment of nonunions: An experiment on dogs. J Surg Res. 1994,57:246～254.
7. W.Schaden, A.Fischer, A.Sailler. Extracorporeal Shock Wave therapy of nonunion or delayed osseous union. Clinical Orthopaedics and related research. 2001,387:90～94.
8．李晓林，余楠生，杜靖远，等．高能震波对骨痂中骨形成蛋白表达
的影响．中华骨科杂志，1999，19：295～298．
9. Joern Ludwig, Sebastian Lauber, Hans-Joachim Lauber, et al. High energe shock wave treatment of femoral head necrosis in adults. Clinical Orthopaedics and related research.. 2001,387:119～123.
10. Yakaoka K, Yoshioka T, Hosoya T, et al. The repair process in experimentally induced avascular necrosis of the femoral head in dogs. Arch Orhop Traumat Surg, 1981,99(2):109～115.
11. Malizos, KN. An experimental canine modal of osteonecrosis: characterization of the repair process. J Orthop Res, 1993,11:350.
12. Matsui M, Saito S, Ohzono K, et al. Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis. [J]. Clin Orthop, 1992,Apr:(277):61～72.
13．杜卓明．实用组织学技术．北京．人民卫生出版社．1981．196～204．
14. Jones JP Jr. Intravascular coagulation and osteonecrosis. Clin orthop, 1992, (277): 41～53.
15. Mont M A, Jones L C, Einhorn T A, et al. Osteonecrosis of the femoral head: Potential treatment with growth and differentiation facter.]. Clin Orthop, 1998,355S:S314～S335.
16. Wang GJ, Sweet DE, Reger SI, et al. Fat-cell changes as a mechanism of avascular necrosis of the necrosis of the femoral head in
cortisone-treated rabbits. J Bone Jiont Surg (Am), 1997,59:729.
17.Wang G J, lennox D W, Reger SI, et al. Cortisone-induced intrafemoral head pressure change and its response to a rilling decompression method [J]. Clin Orthop, 1981,159:274.
18.Glimcher MJ, Kenzora JE. The biology of osteonecrosis of the femoral head and its clinical implication. Clin Orthop. 1979, 140:273.
19.Warner JJP, Philip JH, Brodsky CL, et al. Studies of nontraumatic osteonecrosis. Clin Orthop. 1987, 225:128.
20．何天源，陈诗书．血管内皮生长因子与血管生成．国外医学分子生物学分册，1997，19：236～239．
21.Haupt G, Chvapil M. Effect of shock waves on the healing of partial-thickness wounds in piglets. J Surg Res, 1990,49:45～48.
22.Scheberger R, Sengew T. Non-invasive treatment of long-bone pseucarthrosis by shock waves. Arch Orthop Trauma Surg, 1992, 111:224～227.
23.Valchanou VD, Michailov P. High energy shock waves in the treatment of delayed and nonunion of fractures. Int Orthop. 1991,15:181～184.
24.Valchanou VD, Michailov P, Kerin T, et al. Extracorporeal exposure with shock waves on bone tissue as a factor for local osteogenesis. Endourology. 1991, 5(Suppl 1): 22～26.
25. Ekkernkamp A, Haupt G, Knopf H J, et al. Effects of extracorporeal shock waves on standardized fractures in sheep. Urology, 1991, 145:257～261.
26．郑光，杨刚．高能冲击波对体外血栓溶解影响的实验观察．中国医学生物工程学报，1994，13(1)：49～53．
27．张德俊．超声空化及其生物医学效应．中国超声医学杂志，1995，11(7)：510～512。
28. Morgan TR, Laudone VP, Heston WDW, et al. Free raclical production by high energy shock waves comparison with ionizing irradiation. 1988, 139:186.
29. Galat JA. Oxygen free radicals mediated renal dysfunction. J Surg Res. 1998,46:520.
30．郑华，黄光海，田亚平，等．ESWL前后血和尿的SOD,LPO监测与肾脏损伤的关系．中华泌尿外科杂志，1992，2：123．
31. Evan AP, Willis LP, McAteer JA, et al. Kidney damage and renal function changes are minimized by waveform control that suppressescavitation in shock wave lithotripsy. J Urol. 2002 Oct: 168(4pt 1): 1556～1562.
32．李航，王连志．低能量长间距体外冲击波碎石．临床泌尿外科杂志，1995，10(11)：497～498．
2. Haist J, von Keitz-steeger D, Mohr G, et al. The Orthopaedic Shock wave Therary in the treatment of chronic insertion Tendopathy and Tendinosis Calcarea. In Siebert W, Buch M (eds). Extracorporeal Shock Waves in Orthopaedics. Berlin, Sprnger Verlag. 1997, 159～163.
3. Chaussy C, Eisenberge F, Jocham D, et al (eds). High Energy Shock Wave in medicine. Stuttgart, Thieme. 1997. 235～238.
4. Coombs R, Schaden W, Zhou SSH: Musculoskeletal Shoc Wave Therary. London, Greenwich Medical Media. 2000. 146～152.
5. Haupt A, Haupt G, Ekkernkamp A, et al. Influence of shock waves on fracture healing. Urologe. 1992,31: 43～46.
6. Johannes E J, Kaulesar-Sukul DM, Metura E, et al. High energy shock waves for the treatment of nonunions: An experiment on dogs. J Surg Res. 1994,57:246～254.
7. W.Schaden, A.Fischer, A.Sailler. Extracorporeal Shock Wave therapy of nonunion or delayed osseous union. Clinical Orthopaedics and related research. 2001,387:90～94.
8．李晓林，余楠生，杜靖远，等．高能震波对骨痂中骨形成蛋白表达
的影响．中华骨科杂志，1999，19：295～298．
9. Joern Ludwig, Sebastian Lauber, Hans-Joachim Lauber, et al. High energe shock wave treatment of femoral head necrosis in adults. Clinical Orthopaedics and related research.. 2001,387:119～123.
10. Yakaoka K, Yoshioka T, Hosoya T, et al. The repair process in experimentally induced avascular necrosis of the femoral head in dogs. Arch Orhop Traumat Surg, 1981,99(2):109～115.
11. Malizos, KN. An experimental canine modal of osteonecrosis: characterization of the repair process. J Orthop Res, 1993,11:350.
12. Matsui M, Saito S, Ohzono K, et al. Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis. [J]. Clin Orthop, 1992,Apr:(277):61～72.
13．杜卓明．实用组织学技术．北京．人民卫生出版社．1981．196～204．
14. Jones JP Jr. Intravascular coagulation and osteonecrosis. Clin orthop, 1992, (277): 41～53.
15. Mont M A, Jones L C, Einhorn T A, et al. Osteonecrosis of the femoral head: Potential treatment with growth and differentiation facter.]. Clin Orthop, 1998,355S:S314～S335.
16. Wang GJ, Sweet DE, Reger SI, et al. Fat-cell changes as a mechanism of avascular necrosis of the necrosis of the femoral head in
cortisone-treated rabbits. J Bone Jiont Surg (Am), 1997,59:729.
17.Wang G J, lennox D W, Reger SI, et al. Cortisone-induced intrafemoral head pressure change and its response to a rilling decompression method [J]. Clin Orthop, 1981,159:274.
18.Glimcher MJ, Kenzora JE. The biology of osteonecrosis of the femoral head and its clinical implication. Clin Orthop. 1979, 140:273.
19.Warner JJP, Philip JH, Brodsky CL, et al. Studies of nontraumatic osteonecrosis. Clin Orthop. 1987, 225:128.
20．何天源，陈诗书．血管内皮生长因子与血管生成．国外医学分子生物学分册，1997，19：236～239．
21.Haupt G, Chvapil M. Effect of shock waves on the healing of partial-thickness wounds in piglets. J Surg Res, 1990,49:45～48.
22.Scheberger R, Sengew T. Non-invasive treatment of long-bone pseucarthrosis by shock waves. Arch Orthop Trauma Surg, 1992, 111:224～227.
23.Valchanou VD, Michailov P. High energy shock waves in the treatment of delayed and nonunion of fractures. Int Orthop. 1991,15:181～184.
24.Valchanou VD, Michailov P, Kerin T, et al. Extracorporeal exposure with shock waves on bone tissue as a factor for local osteogenesis. Endourology. 1991, 5(Suppl 1): 22～26.
25. Ekkernkamp A, Haupt G, Knopf H J, et al. Effects of extracorporeal shock waves on standardized fractures in sheep. Urology, 1991, 145:257～261.
26．郑光，杨刚．高能冲击波对体外血栓溶解影响的实验观察．中国医学生物工程学报，1994，13(1)：49～53．
27．张德俊．超声空化及其生物医学效应．中国超声医学杂志，1995，11(7)：510～512。
28. Morgan TR, Laudone VP, Heston WDW, et al. Free raclical production by high energy shock waves comparison with ionizing irradiation. 1988, 139:186.
29. Galat JA. Oxygen free radicals mediated renal dysfunction. J Surg Res. 1998,46:520.
30．郑华，黄光海，田亚平，等．ESWL前后血和尿的SOD,LPO监测与肾脏损伤的关系．中华泌尿外科杂志，1992，2：123．
31. Evan AP, Willis LP, McAteer JA, et al. Kidney damage and renal function changes are minimized by waveform control that suppressescavitation in shock wave lithotripsy. J Urol. 2002 Oct: 168(4pt 1): 1556～1562.
32．李航，王连志．低能量长间距体外冲击波碎石．临床泌尿外科杂志，1995，10(11)：497～498．