川骨片防治激素性股骨头坏死实验研究
|
摘要
目的
本研究通过测定BMP-2、bFGF、VEGF、Bcl-2、甘油三脂、血浆粘度在激素造摸致股骨头坏死的兔股骨头组织及血清中的表达,研究中药川骨片对激素造摸致股骨头坏死中的影响,深入探讨川骨片对激素性股骨头坏死中成骨细胞、微血管修复、抗凋亡、血脂、血流变学的影响,及其对上述影响产生的信号传导途径和调节系统机制的分子作用机制的探索。
方法
采用Miyanishi方法造模,甲强龙20mg/kg体重臀部肌注,每周2次,同时肌注青霉素16万U和链霉素15万U预防感染。将日本大耳兔分为5组,正常组(12只)、模型组(12只)、阳性对照组(12只)、高剂量组(12只)、低剂量组(12只)；除正常组外,其余各组给予甲基强的松龙20mg/kg体重臀部肌注,每周2次,同时肌注青霉素16万U和链霉素15万U预防感染,川骨片高剂量组每天0.9g／1kg体重.ml／d灌胃；川骨片低剂量组为每天0.3g／1kg体重.ml／d灌胃。对照组左归丸每组给药为1.5g／1kg体重.ml／d灌胃。模型组给予蒸馏水1ml/1kg体重／d灌胃。42天后处死动物,采用组织病理学观察和免疫组织化学方法检测,分析BMP-2、bFGF、VEGF、Bcl-2的表达。同时送检血清甘油三脂、血浆粘度。
结果
一般状态：42天末正常组同实验前,模型组结束时兔毛干枯脱落蓬乱,活动摄饮均减少,川骨片高剂量和阳性对照组状态较模型组好。
HE染色结果：模型组呈现骨细胞核固缩,部分核消失,空骨陷窝数较多,坏死骨小梁变细,骨小梁数目减少,毛细血管扩张、淤血,脂肪细胞增大增多,细胞间质出现大量胶原纤维,并有断裂。川骨片高剂量和阳性对照组骨细胞核固缩减少,空骨陷窝数少,部分骨小梁周围成骨细胞缺失,毛细血管扩张、造血细胞增多,脂肪细胞增多明显,细胞间质出现胶原纤维。
股骨头组织免疫组化测定结果：BMP-2、bFGF、VEGF、Bcl-2的免疫组化染色阳性物质均呈棕黄色,显微镜下观察：Bcl-2的阳性物质从川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组、正常组有逐渐减少的侵蚀；BMP-2、bFGF、VEGF的阳性物质从模型组、川骨片低剂量组、阳性对照组、川骨片高剂量组、正常组有逐渐增加的趋势。免疫组化染色的阳性物质经经Image-Pro Plus 6.0专业图象分析软件分析量化：川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组与正常组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05)；川骨片高剂量组、阳性对照组、川骨片低剂量组与模型组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05),川骨片高剂量组、阳性对照组与川骨片低剂量组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05)；川骨片高剂量组与阳性对照组(BMP-2、bFGF、VEGF、Bcl-2)比较,无统计学意义(P>0.05)。
甘油三脂和血浆粘度检测结果；与模型组比较,血清VP、S-TG的表达明显下降(P<0.05)；川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组与正常组比较血清VP、S-TG的表达有差异(P<0.05),川骨片高剂量组、阳性对照组川与川骨片低剂量组比较血清VP、S-TG的表达有差异(P<0.05)；川骨片高剂量组与阳性对照组川比较VP、S-TG的表达无统计学意义(P>0.05)。
结论
本研究在成功建立甲强龙诱导日本大耳白兔的股骨头坏死模型的基础上,探讨了中药川骨片对该模型的影响。研究发现：中药川骨片促进成骨细胞的分化增殖、促进微血管的生长、保护骨细胞、促进骨的修复重建。其作用机制可能与川骨片的以下作用有关：通过调节BMP-2、bFGF的表达,促进成骨细胞的分化增殖；调控VEGF的表达,促进骨组织的微血管增生,促进Bcl-2的表达,保护骨细胞。降低甘油三脂和血浆粘度,可增加股骨头血供。
Objective
The steroid-induced necrosis of the femoral head was high in the whole world.One of the results of necrosis of the femoral head is osteoarthritis if it isn't treat effectively. The necrosis of the femoral head was reversible through appropriate treatment in the early.This experiment studied the effect of the Traditional Chinese Medicine called Chuangu tablets on the expression of BMP-2,FGF,VEGF,Bcl-2, VP、TGin the bony tissue of necrosis of the femoral head and serum of the rabbits which were induced by subcutaneous injectin of methylprednisolone sodium succinate.To investigate the effects of Traditional Chinese Medicine Chuangu tablets on the experimental necrosis of the femoral head induced by methylprednisolone sodium succinate in the rabbits.Further to evaluate the prosthetic effects of Chuangu tablets on the bony tissue of necrosis of the femoral head, remodel the femoral head,and explore its possible bone remodeling molecular mechhanisma on both Signal Transduction Pathway.
Methods
Necrosis of the femoral head was induced in rabitts by subcutaneous injectin of methylprednisolone sodium succinate.Sixty rabitts were randomly divided into 5 group; normal control group(N group,12 rabitts), model control group(M group,12 rabitts),positive control group(P group,12 rabitts),high dose of Chuangu Tablet(H group,12 rabitts), low dose of Chuangu Tablet(L group,12 rabitts),The rabbits of M,P,H and L group were disposed with injection of solumedrol injection 20mg/kg,once 3 days,at the time H and L groups were treated with Chuangu tablets,once Iday,and Pgroup was treated with Zhuogui pills,once 1 day.42 days later,all the rabbits were sacrificed.The pathological change of the femoral head were observed by HE staining under microscope.The protein expression of VEGF and BMP-2 were determinged by immunohistochemical staining method.Serum levels of VP and TG were dectected.
.Results:
General status:At the end of 42 days normal control group was unchanged.The fur color pattern inmodel control group got parched unkempt,the activity and cibation reduced. The status between the high dose of Chuangu tablets group and positive control group were better than that of model control group.
HE stain for the bony tissue:In the model control group, Empty lacunaes increased Liposome was found in the cytoplasm and nuclei of the osteocyte in early period.Pyknosis,karyolysis and karyorrhexis were observed in the osteocyte..There was obviously lipid droplet.The structure of plasma menbrans was not complete, obvious screvice could be found in collagenous fiber.But, in the high dose of Chuangu tablets group and positive control group, Empty lacunaes increasing wan in slight extent. Pyknosis,karyolysis and karyorrhexis were not obviously observed in the osteocyte.
Immunohistochemisty stain for the bony tissue:Buffy represents positive result.. The normal control group is the most obvious by the positive mass of BMP-2,FGF and VEGF.The positive mass of BMP-2,FGF and VEGF increased gradually in the order of model control group, low dose of Chuangu Tablet group, positive control group(P group,high dose of Chuangu Tablet, normal control group.But, the positive mass of Bcl-2 decreased gradually in the order of model control group, low dose of Chuangu Tablet group, positive control group(P group,high dose of Chuangu Tablet, normal control group.
The data from immunohistochemistry are puantitied by Image-Pro Plus 6.0 analysis program. BMP-2,FGF and VEGF of the model control group, low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the normal control group (P<0.05).And those masses of the low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the model control group (P<0.05). those masses of positive control group,high dose of Chuangu Tablet is significantly different from low dose of Chuangu Tablet group.Regarding of the high dose of Chuangu Tablet and positive control group,there is not significantly different between (P>0.05).
VP and TG:Compared with the model control group,,serumVPA and TG (P< 0.05) were significantly different from low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet, normal control group. Serum TG and VP of low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the normal control group (P<0.05). Serum TG and VP of low dose of Chuangu Tablet group is significantly different from positive control group,high dose of Chuangu Tablet (P< 0.05). Regarding of the high dose of Chuangu Tablet and positive control group,there is not significantly different between (P>0.05).
Conclusion
This experiment researches the effects of Traditional Chinses Medicine Chuangu Tablets on the prevention and cure of steroid-induced necrosis of the femoral head in rabitts.The study reveals:Traditional Chinses Medicine Chuangu Tablets not only have a protective effect on steroid-induced necrosis of the femoral head and can definitely inhibit development byt necrosis of bony tissue,but also promote the prosthetic effects of Chuangu tablets on the bony tissue of necrosis of the femoral head, remodeling the femoral head.The possible remodeling the femoral head molecular mechanisms of the effects of Chuangu Tablets decoction may due to up-regulating expression of BMP-2、bFGF、VEGF、Bcl-2; up-regulating Expression of BMP-2、bFGF Signal Transduction Pathway can promote osteoblasts multiplication and differentiation;VEGF Signal Transduction Pathway can promote differentiation of epithelial cells in micrangium of the femoral head; Bcl-2 Signal Transduction Pathway is anti-apoptosis of bony cell. Moreover, Chuangu Tablets can regulate fat metabolism and rheology of the blood. Chuangu tablets can promote the expression level of VEGF and BMP-2 of callus tissue in steroid-induced necrosis of the femoral head, This may be one of the mechanisms of Chuangu tablets to prevention and cure of steroid-induced necrosis of the femoral head. protein
本研究通过测定BMP-2、bFGF、VEGF、Bcl-2、甘油三脂、血浆粘度在激素造摸致股骨头坏死的兔股骨头组织及血清中的表达,研究中药川骨片对激素造摸致股骨头坏死中的影响,深入探讨川骨片对激素性股骨头坏死中成骨细胞、微血管修复、抗凋亡、血脂、血流变学的影响,及其对上述影响产生的信号传导途径和调节系统机制的分子作用机制的探索。
方法
采用Miyanishi方法造模,甲强龙20mg/kg体重臀部肌注,每周2次,同时肌注青霉素16万U和链霉素15万U预防感染。将日本大耳兔分为5组,正常组(12只)、模型组(12只)、阳性对照组(12只)、高剂量组(12只)、低剂量组(12只)；除正常组外,其余各组给予甲基强的松龙20mg/kg体重臀部肌注,每周2次,同时肌注青霉素16万U和链霉素15万U预防感染,川骨片高剂量组每天0.9g／1kg体重.ml／d灌胃；川骨片低剂量组为每天0.3g／1kg体重.ml／d灌胃。对照组左归丸每组给药为1.5g／1kg体重.ml／d灌胃。模型组给予蒸馏水1ml/1kg体重／d灌胃。42天后处死动物,采用组织病理学观察和免疫组织化学方法检测,分析BMP-2、bFGF、VEGF、Bcl-2的表达。同时送检血清甘油三脂、血浆粘度。
结果
一般状态：42天末正常组同实验前,模型组结束时兔毛干枯脱落蓬乱,活动摄饮均减少,川骨片高剂量和阳性对照组状态较模型组好。
HE染色结果：模型组呈现骨细胞核固缩,部分核消失,空骨陷窝数较多,坏死骨小梁变细,骨小梁数目减少,毛细血管扩张、淤血,脂肪细胞增大增多,细胞间质出现大量胶原纤维,并有断裂。川骨片高剂量和阳性对照组骨细胞核固缩减少,空骨陷窝数少,部分骨小梁周围成骨细胞缺失,毛细血管扩张、造血细胞增多,脂肪细胞增多明显,细胞间质出现胶原纤维。
股骨头组织免疫组化测定结果：BMP-2、bFGF、VEGF、Bcl-2的免疫组化染色阳性物质均呈棕黄色,显微镜下观察：Bcl-2的阳性物质从川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组、正常组有逐渐减少的侵蚀；BMP-2、bFGF、VEGF的阳性物质从模型组、川骨片低剂量组、阳性对照组、川骨片高剂量组、正常组有逐渐增加的趋势。免疫组化染色的阳性物质经经Image-Pro Plus 6.0专业图象分析软件分析量化：川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组与正常组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05)；川骨片高剂量组、阳性对照组、川骨片低剂量组与模型组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05),川骨片高剂量组、阳性对照组与川骨片低剂量组(BMP-2、bFGF、VEGF、Bcl-2)比较,有显著差异(P<0.05)；川骨片高剂量组与阳性对照组(BMP-2、bFGF、VEGF、Bcl-2)比较,无统计学意义(P>0.05)。
甘油三脂和血浆粘度检测结果；与模型组比较,血清VP、S-TG的表达明显下降(P<0.05)；川骨片高剂量组、阳性对照组、川骨片低剂量组、模型组与正常组比较血清VP、S-TG的表达有差异(P<0.05),川骨片高剂量组、阳性对照组川与川骨片低剂量组比较血清VP、S-TG的表达有差异(P<0.05)；川骨片高剂量组与阳性对照组川比较VP、S-TG的表达无统计学意义(P>0.05)。
结论
本研究在成功建立甲强龙诱导日本大耳白兔的股骨头坏死模型的基础上,探讨了中药川骨片对该模型的影响。研究发现：中药川骨片促进成骨细胞的分化增殖、促进微血管的生长、保护骨细胞、促进骨的修复重建。其作用机制可能与川骨片的以下作用有关：通过调节BMP-2、bFGF的表达,促进成骨细胞的分化增殖；调控VEGF的表达,促进骨组织的微血管增生,促进Bcl-2的表达,保护骨细胞。降低甘油三脂和血浆粘度,可增加股骨头血供。
Objective
The steroid-induced necrosis of the femoral head was high in the whole world.One of the results of necrosis of the femoral head is osteoarthritis if it isn't treat effectively. The necrosis of the femoral head was reversible through appropriate treatment in the early.This experiment studied the effect of the Traditional Chinese Medicine called Chuangu tablets on the expression of BMP-2,FGF,VEGF,Bcl-2, VP、TGin the bony tissue of necrosis of the femoral head and serum of the rabbits which were induced by subcutaneous injectin of methylprednisolone sodium succinate.To investigate the effects of Traditional Chinese Medicine Chuangu tablets on the experimental necrosis of the femoral head induced by methylprednisolone sodium succinate in the rabbits.Further to evaluate the prosthetic effects of Chuangu tablets on the bony tissue of necrosis of the femoral head, remodel the femoral head,and explore its possible bone remodeling molecular mechhanisma on both Signal Transduction Pathway.
Methods
Necrosis of the femoral head was induced in rabitts by subcutaneous injectin of methylprednisolone sodium succinate.Sixty rabitts were randomly divided into 5 group; normal control group(N group,12 rabitts), model control group(M group,12 rabitts),positive control group(P group,12 rabitts),high dose of Chuangu Tablet(H group,12 rabitts), low dose of Chuangu Tablet(L group,12 rabitts),The rabbits of M,P,H and L group were disposed with injection of solumedrol injection 20mg/kg,once 3 days,at the time H and L groups were treated with Chuangu tablets,once Iday,and Pgroup was treated with Zhuogui pills,once 1 day.42 days later,all the rabbits were sacrificed.The pathological change of the femoral head were observed by HE staining under microscope.The protein expression of VEGF and BMP-2 were determinged by immunohistochemical staining method.Serum levels of VP and TG were dectected.
.Results:
General status:At the end of 42 days normal control group was unchanged.The fur color pattern inmodel control group got parched unkempt,the activity and cibation reduced. The status between the high dose of Chuangu tablets group and positive control group were better than that of model control group.
HE stain for the bony tissue:In the model control group, Empty lacunaes increased Liposome was found in the cytoplasm and nuclei of the osteocyte in early period.Pyknosis,karyolysis and karyorrhexis were observed in the osteocyte..There was obviously lipid droplet.The structure of plasma menbrans was not complete, obvious screvice could be found in collagenous fiber.But, in the high dose of Chuangu tablets group and positive control group, Empty lacunaes increasing wan in slight extent. Pyknosis,karyolysis and karyorrhexis were not obviously observed in the osteocyte.
Immunohistochemisty stain for the bony tissue:Buffy represents positive result.. The normal control group is the most obvious by the positive mass of BMP-2,FGF and VEGF.The positive mass of BMP-2,FGF and VEGF increased gradually in the order of model control group, low dose of Chuangu Tablet group, positive control group(P group,high dose of Chuangu Tablet, normal control group.But, the positive mass of Bcl-2 decreased gradually in the order of model control group, low dose of Chuangu Tablet group, positive control group(P group,high dose of Chuangu Tablet, normal control group.
The data from immunohistochemistry are puantitied by Image-Pro Plus 6.0 analysis program. BMP-2,FGF and VEGF of the model control group, low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the normal control group (P<0.05).And those masses of the low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the model control group (P<0.05). those masses of positive control group,high dose of Chuangu Tablet is significantly different from low dose of Chuangu Tablet group.Regarding of the high dose of Chuangu Tablet and positive control group,there is not significantly different between (P>0.05).
VP and TG:Compared with the model control group,,serumVPA and TG (P< 0.05) were significantly different from low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet, normal control group. Serum TG and VP of low dose of Chuangu Tablet group, positive control group,high dose of Chuangu Tablet is significantly different from the normal control group (P<0.05). Serum TG and VP of low dose of Chuangu Tablet group is significantly different from positive control group,high dose of Chuangu Tablet (P< 0.05). Regarding of the high dose of Chuangu Tablet and positive control group,there is not significantly different between (P>0.05).
Conclusion
This experiment researches the effects of Traditional Chinses Medicine Chuangu Tablets on the prevention and cure of steroid-induced necrosis of the femoral head in rabitts.The study reveals:Traditional Chinses Medicine Chuangu Tablets not only have a protective effect on steroid-induced necrosis of the femoral head and can definitely inhibit development byt necrosis of bony tissue,but also promote the prosthetic effects of Chuangu tablets on the bony tissue of necrosis of the femoral head, remodeling the femoral head.The possible remodeling the femoral head molecular mechanisms of the effects of Chuangu Tablets decoction may due to up-regulating expression of BMP-2、bFGF、VEGF、Bcl-2; up-regulating Expression of BMP-2、bFGF Signal Transduction Pathway can promote osteoblasts multiplication and differentiation;VEGF Signal Transduction Pathway can promote differentiation of epithelial cells in micrangium of the femoral head; Bcl-2 Signal Transduction Pathway is anti-apoptosis of bony cell. Moreover, Chuangu Tablets can regulate fat metabolism and rheology of the blood. Chuangu tablets can promote the expression level of VEGF and BMP-2 of callus tissue in steroid-induced necrosis of the femoral head, This may be one of the mechanisms of Chuangu tablets to prevention and cure of steroid-induced necrosis of the femoral head. protein
引文
1 Jones JP jr.Etiology and pathogenesis of osteonecrtosis[J].J Clin Orthop,1994,14:153-155.
2张鹤山,李子荣.股骨头坏死诊断与治疗的专家建议[J].中华骨科杂志 2007,27(2)：146-148.
3徐传毅,何伟,李雄.从“瘀血”理论辨识股骨头坏死[J].中国中医基础医学杂志,2002,8(5)：18-19.
4宋剑南.从生物化学角度看痰及痰瘀相关[J].中国中医基础医学杂志,2000,6(3)：40-43.
5刘少军,袁浩.股骨头坏死的中医临床思路与方法探究[J].中国医药学报2002,17(1)：44-47.
6孙材康,娄志强,高建中,等.中医药治疗股骨头缺血性坏死[J].河南中医1996；16(1)：32.
7张铁刚,章艳霞,李敏,等.股骨头坏死中医三型分治的临床总结[J].中国中西医结合外科杂志1998；4(6)：354.
8诸福度,崔明,吴材康,等.股骨头缺血坏死的中医药治疗[J].中国骨伤1994；7(6)：46.
9马素英.马氏骨片治疗股骨头坏死128例X线变化[J].中国骨伤1996；9(4)：23.
10邓沂,张晓刚,任远,等.中医对股骨头坏死的认识[J].甘肃中医学院学报 1998；15(4)：54.
11陈卫衡,刘道兵,张洪美,等.股骨头坏死的三期四型辨证思路[J].中国中医基础医学杂志2003；9(12)：51.
12杜国辉,刘德玉.骨复生对激素性家兔股骨头坏死血清中骨形态发生蛋白-2及转化生长因子-β影响的实验研究[J].陕西中医学院学报2006,29(3).
13刘日光,沈冯君,尹培荣,易诚青.中药对股骨头缺血坏死修复过程中血管内皮生长因子基因表达的影响[J].中国骨伤2004,17(12)：705-707.
14李景田,邹锦慧,张慧明,黄伟,周小璜,李伯灵,陈秀琴.预防用药对激素性股骨头坏死骨细胞凋亡的影响[J].中国临床康复2006,10(27)：168-171.
15田伟明,王文智,王鑫国.骨复活汤对激素性股骨头坏死血液流变学及脂代谢的影响[J].中国中药杂志,2002,27(10)：769～771.
16刘宏泽,王文瑞,卫小春,张剑宇.丹参与骨碎补注射液防治激素诱发股骨头坏死的实验研究[J].中国骨伤2003,16(12)：726-728.
17张弛,杨志伟,朱明双等.活血通络法对激素性股骨头坏死家兔模型的组织形态学影响[J].新医科大学学报2007,30(5)：452-454.
18Miyanishi K,Yamamoto T,Irisa T,Motomura G,Jingushi S,Sueis K,Iwamoto Y.Effects of different corticosteroids on the develoment of osteonecrosis in rabbits[J].J Rheumatology (Oxford) 2004,4(3):332～336.
19陈彦华,殷惠芳,王式鲁.马血清加激素诱导股骨头缺血性坏死动物模型的实验研究[J].山东中医药大学学报,2003,27：222-223.
20刘万林,郭文通,李文琪,等.激素性股骨头缺血性坏死动物模型诱导[J].内蒙古医学院学报,1986；20(2)：71.
21 Mastsui M,Saito S,Ohzoao K,et al.Experimental steroid-induced osteo-necrosis in adult rabbit with hypersensitive vasculitis [J].J Clin orthop.1992,277:61.
22马在山.马氏秘传骨丸治疗股骨头无菌性坏死临床疗效观察[J] 北京中医杂志,1989(1)：48.
23宋剑南,刘东远,牛晓红等.高脂血症与中医痰浊关系的实验研究[J].中国中医基础医学杂志,1995,1：49-50.
24郭宏昌,牛晓亚,张向东.痰浊证与血脂水平关系的研究[J].河南中医药学刊,1998,13(6)：18-19.
25李岩,赵雁,黄启福等.中医络病的现代认识[J].北京中医药大学学报,2002,25(3)：1-5.
26于世凤.骨吸收与骨形成[J].现代康复,2001,5(2)：10..
27苗明三.法定中药药理与临床(第一版)[M].世界图书出版社,1998
28 Lee MH,Kim YJ,Kim HJ,et al. BMP-2-induced runx2 expression is mediated by Dlx5, and TGF-1 Opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression [J]. Biol Chem,2003,278(36):34387-34394.
29 Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM:BMP-2-induced Osterix expression is mediated by DIx5 but is independent of Runx2[J]. Biochem Biophys Res Commun 2003,309:689-694.
30 Choi KY, Kim HJ,Lee MH,et al. Dev Dyn,2005;233(1):115-121
31 Rengachary MD, Bone morphogenetic protein basic connects [J].Neurosurg Focus,2002,13(12):l.
32 Nohe A,Keating E,Underhill T M,et al.Effect of the distribution and clustering of the type I A BMP receptor(ALK3) with the type II BMP receptor on the activationg of signaling path ways[J].J Cell Set 2003,116(pt 16):3277-3284.
33 Sow H,Kaji H,Hendy G N et al.Menin is required for bone morphogenetic protein-2 and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smad and Runx2[J]. J Biol Chem,2004,279(39):40267-40278.
34 Iwasaki S,Iguchi M,Watanabe K,et al.Specific activation of the p38 mitogen-activated protein kinase sigaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2 [J].J Bool Chem,1999,274(37):26503-26510.
35 Lemonnier J, Ghayor C, Guicheux J, et al.Protein kinase C-independent activation of protein kinase D is involved in BMP-2-induced activation of stress mitogen-activated protein kinases JNK and p38 and osteoblastic cell differentiation[J]. J Biol Chem,2004,279(1):259-264.
36 Ohyama Y, Nifuji A, Maeda Y, et al. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis[J]. Endocrinology,2004,145(10):4685-4692.
37 Arikawa T, Omura K, Morita I. Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells[J]. J Cell Physiol,2004,200(3):400-406.
38 Ohyama Y, Nifuji A, Maeda Y, et al. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis [J]. Endocrinology,2004,145(10):4685-4692.
38Cheng H, Jiang W, Phillips F M, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs) [J]. J Bone Joint Surg Am,2003,85-A(8):1544-1552.
40Jorgensen N R, Henriksen Z, Sorensen O H, et al. Dexamethasone,BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype:validation of an in vitro model for human bone marrow-derived primary osteoblasts[J]. Steroids,2004,69 (4):219-226.
41 Osyczka A M, Diefenderfer D L, Bhargave G, et al. Different effects of BMP-2 on marrow stromal cells from human and rat bone[J]. Cells Tissues Organs,2004,176(13):109-119.
42 Dragoo J L, Choi J Y, Lieberman J R, et al. Bone induction by BMP-2 transduced stem cells derived from human fat [J]. J Orthop Res,2003,21(4):622-629.
43 Akita S, Fukui M, Nakagawa H, et al. Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor[J]. Wound Repair Regen,2004,12(2):252-259.
44 Huang W, Carlsen B, Wulur I, et al. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold[J]. Exp Cell Res,2004,299(2):325-334.
45 Huang W, Carlsen B, Wulur I, et al. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold[J]. Exp Cell Res,2004,299(2):325-334.
46 Bessho K, Carnes D L, Cavin R, et al. Experimental studies on bone induction using low-molecular-weight poly (DL-lactide-co-glycolide)as a carrier for recombinant human bone morphogenetic protein-2[J]. J Biomed Mater Res,2002,61(1):61-65.
47 Woo B H, Fink B F, Page R, et al. Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2in a polymeric matrix[J]. Pharm Res,2001,18(12):1747-1753.
48 Yamamoto M, Takahashi Y, Tabata Y. Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein [J]. Biomaterials,2003,24 (24):4375-4383.
49 Maeda H, Sano A, Fujioka K. Profile of rhBMP-2 release from collagen minipellet and induction of ectopic bone formation[J]. Drug Dev lnd Pharm,2004,30 (5):473-480.
50 Yang X B, Whitaker M J, Sebald W, et al. Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds[J]. Tissue Eng,2004,10(7-8):1037-1045.
51 Okubo Y, Bessho K, Fujimura K, et al. In vitro and in vivo studies of a bone morphogenetie protein-2 expressing adenoviral vector [J]. J Bone Joint Surg Am,2001,83-A Suppl 1 (Pt 2):S99-S104.
52 Xing W, Baylink D, Kesavan C, et al. HSV-1 amplicon-mediated transfer of 128-kb BMP-2 genomic locus stimulates osteobla st differentiation in vitro[J]. Biochem Biophys Res Commun,2004,319 (3):781-786.
53 Prats H, Kaghad M, Prats AC, Klagsbrun M, Lelias JM, Liauzun P et al. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons[J]. J Proc Natl Acad Sci USA, 1989,86:1836-1840.
54 Eriksson AE, Cousens LS, Weaver LH, Matthews BW 1991 Three-dimensional structure of human basic fibroblast growth factor[J]. Proc Natl Acad Sci USA,1991,88:3441-3445.
55 Kiefer MC,Stephans JC,Crawford K,et al.Ligand-affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor [J]. Proc Natl Acad Sci USA,1990,87:69854.
56 Luo Y,Lu W,Mohamedali KA,et al.The glyeine box:a determinant of specificity for fibroblaat growth factor[J].Bio chemistry,1998,37(7):1 6506-15.
57 Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P. Murine FGFR-1 is required for early postimplantation growth and axial organization[J]. Genes Dev.1994; 8:3045-3057.
58 Arman E.Haffner-Krausz R,Chen Y,et al.Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development[J].Proc Natl Acad Sci USA,1998,95(9):5082-5087.
59 Shiang R,Thompson LM,Zhu YZ,et al.Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism,achondroplasia[J].Cell.1994,78:335-342.
60 Peters KG, Marie J,Wilson E,et al.Point mutation an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogeneses [J].Nature,1992,358:678-680.
61 Hadari YR,Kouhara H,Lax I,et al.Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation [J].Mol Cell Biol,1998,18:3966.
62 Xu H,Lee KW,Goldfarb MR.Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins [J].J Biol Chem,1998,273:17987-17989. 63 Weinstein DC,Marden J,Camevali F.FGF-mediated mesoderm induction involves the Src-family kinase Laloo [J].Nature,1998,304:904.
64 Klint P,Kanda S,Kloog Y,et al.Contribution of Src and Ras pathways in FGF-2 induced endothelial cell differentiation [J].Oncogene,1999,18:3354.
65 Brighton CT.Principles of fracture healing.In:cornell CN, Lane JM.Newest factors in fracture healing [J].Clin Orthop,1992,277:297-312.
66 Canalis E,Centrella M,Mccarthy T.Effects of basic fibroblast growth factor on bone formation in vitro[J].J Clin Invest,1988,81:1572-1577.
67 Kotev-Emeth S,Savion N.Effect of maturation on the osterogenic response of cultured stromal bone marrow cells to basic fibroblast growth factor[J].Bone,2000,27(6):777-783.
68 Bolander ME.Regulation of fracture repai rby growth factors [J].Proc Soc Exo Bio Med,1992,200:165-170.
69Niswandr L,Martin G, FGF4 and BMP have opposite effects on limb growth [J].Nature,1993,361:68-71.
70 Seghezzi G,PatelS,Ren CJ,et al.Fibroblast growth factor-2(FGF22) induces vascular endothelial growthfactor(VEGF) expression in the endothelial cells of forming capillaries:anautocrine mechanism contributing to angiogenesis [J].J Cell Biol,1998,141:1659.
71王海彬,何伟,袁浩.成骨细胞和型胶原[J].Chinese Trad Med Traum&Orthop,2003,11(3):56-59.
72 Risau W. Mechanisms of angiogenesis [J].Nature,1997,386(6626):671-674., Carmeliet P. Mechanisms of angiogenesis and arteriogenesis [J]. Nat Med,2000,6(4):389-395.
73 Asahara T, Takahashi T, Masuda H, et al.VEGF contributes to postnatal neovascularization by mobilizing bone marrow-rived endothelial progenitor cells [J]. EMBO J,1999,18 (14):3964-3972.
74 Darland D C, D' more P A. Blood vessel maturation:vascular development comes of age[J]. J Clin Invest,1999, 103(2):157-158.
75 Ohta H, Ishiyama J, Saito H, et al. Effects of pretreatment with basic fibroblast growth factor, epidermal growth factor and nerve growth factor on neuron survival and neovascularization of superior cervical ganglion transplanted into the third ventricle in rats[J]. Jpn J Pharmacol,1991,55(2):255-262.
76 Galiano R D, Tepper O M, Pelo C R, et al.Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells[J]. Am J Pathol,2004,164(6):1935-1947.
77 Soker S. Neuropilin in the midst of cell migration and retraction[J].Int J Biochem Cell Biol,2001,33(4):433-437.
78 Veikkola T, Alitalo K. VEGFs receptors and angiogenesis[J]. Semin Cancer Biol,1999,9(3):211-220.
79 Soker S, Takashima S, Miao H Q, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor[J]. Cell,1998,92(6):735-745.
80 Eckardt H, Bundgaard K G, Christensen K S, et al. Effects oflocally applied vascular endothelial growth factor (VEGF) and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis [J]. J Orthop Res,2003,21(2): 335-340:
81 Gu F, Amsden B, Neufeld R. Sustained delivery of vascular endothelial growth factor with alginate beads[J] J Control Release,2004,96 (3):463-472.
82 Murphy W L, Peters M C, Kohn D H, et al. Sustained release of vascular endothelial growth factor from mineralized poly (lactide-co-glycolide) scaffolds for tissue engineering[J]. Biomaterials,2000,21(24):2521-2527.
83 Murphy W L, Simmons C A, Kaigler D, et al. Bone regeneration via a mineral substrate and induced angiogenesis[J]. J Dent Res,2004,83(3):204-210.
84 Richardson T P, Peters M C, Ennett A B, et al. Polymeric system for dual growth factor delivery[J]. Nat Biotechnol,2001,19 (11):1029-1034.
85 Zisch A H, Lutolf M P, Ehrbar M, et al.Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth[J]. FASEB J,2003,17 (15):2260-2262.
86 Soker S, Machado M, Atala A. Systems for therapeutic angiogenesis in tissue engineering[J]. World J Urol, 2000,18(1):10-18.
87 Wu X, Rabkin Aikawa E, Guleserian K J, et al.Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells[J]. Am J Physiol Heart Circ Physiol,2004,287 (2):H480-H487.
88 Wijelath E S, Rahman S, Murray J, et al.Fibronectin promotes VEGF-induced CD34 cell differentiation into endothelial cells[J]. J Vasc Surg,2004,39 (3):655-660.
89 Kubo K, Kuroyanagi Y. Characterization of a cultured dermal substitute composed of a spongy matrix of hyaluronic acid and collagen combined with fibroblasts[J]. J Artif Organs,2003,6(2):138-144.
90Kaigler D, Krebsbach P H, Polverini P J, et al. Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells[J]. Tissue Eng,2003,9 (1):95-103.
91 Street J, Bao M, deGuzman L, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover[J]. Proc Natl Acad Sci U S A,2002,99(15):9656-9661.
92 Chang CS, Su CY, Lin TC. Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts[J]. J Biomed Mater Res,1999,48(4):411-416.
93 Lu Y, Shansky J, Del Tatto M, et al. Recombinant vascular endothelial growth factor secreted from tissue-engineered bioartificial muscles promotes localized angiogenesis[J]. Circulation,2001,104 (5):594-599.
94Thompson CB.Apoptosis in the pathogenesis and treatment of disease [J].Science,1995,267:1456-1462.
95 Tsujimoto Y,Cossman J,Jaffe E,et al. Involvement of the bcl-2 gene in human follicular lymphoma[J].Science,1985,228:1440-1443.
96Reed JC.Mechanisms of apoptosis[J].Am JPathol,2000,157:1415-1430.
97Adams JM,Cory S.The Bcl-2 protein family:arbiters of cell survival[J].Science,1998,281:1322-1326.
98Green DR,Reed JC.Mitochondria and apoptosis [J].Science,1998,2811309-1312.
99Wolter KG,Hsu YT,Smith CL,et al.Movement of Bax from the cytosol to mitochondria during apoptosis[J].J Cell Biol,1997,139:1281-1292.
100 Oltvai ZN,Milliman CL,Korsmeyer SJ.Bcl-2 heterodimerizes in vivo with a conserved homolog,Bax,that accelerates programmed cell death[J]. Cell,1993,74:609-619.
101 Sato T,Hanada M,Bodrug S,et al.Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system[J].Proc Natl Acad Sci USA,1994,91:9238-9242.
102Muchmore SW,Sattler M,Liang H,et al.Links X-ray and NMR structure of human Bcl-XL,aninhibitor of programmed cell death[J].Nature,1996,381:335-341.
103李楠,王和鸣.体外培养成骨细胞研究新进展[J].中国骨伤,2003,16(3)：187-189.
104Edward PJ.Osteotoxicology:the role of lead in bone diseases[J]. Curr Opin Orthop,2000,11(5):360-365.
105Sato M,et al.Apoptosis and expression of stress protein during development of ischaemic osteonecrosis in the rat [J]. J Bone Joint Surg Br 2001,83(5):751-759.
106胡野,凌志强,单小云主编.细胞凋亡的分子医学[M].北京军事医学科学出版社,2002.62-70.
107李靖,王权平,张颖.Bcl-2 过表达对 TNF2A 诱导大鼠成骨细胞凋亡的影响[J].中国骨质疏松杂志,2003,9(4)：295-298.
108何伟,方斌,庞智辉,等.激素性股骨头坏死的早中期超微结构观察[J].中医正骨,2000,12(7)：4.
109贺西京,毛履真,王坤正,等.肾上腺皮质激素引起股骨头缺血性坏死的机制实验研究[J].中华骨科杂志,1992,12(6)：440.
110贺西京,毛履真,王坤正,等.激素性股骨头坏死与骨细胞脂肪变性的实验研究[J].中华骨科杂志,1996,16(1)：45.
111孙强,施裕新,等.激素性股骨头坏死发病机制的实验研究[J].中国临床医学,2003,10(4)：465.
112 Jines JP.Intravascular coagulation and osteonecrosisc [J].Clin Orthop,1992,277:41.
113袁浩,李雄,何伟,等.生脉成骨胶囊预防激素性股骨头缺血性坏死的实验研究[J].中国中医骨伤,1999,7(4)：4-8.
114赵万军,肖鲁伟,董培建.激素诱导股骨头缺血性坏死的发病机理及中医药的防治[J].中国中医骨伤科杂志,1998,6(3)：50.
115Starklink H,Lausten GS,Amoldi CC.Microvascular obstruction invascular necrosis,immunohistochmistry of 14 femoral headc[J].Acta Orthop Scand,1995,66:9.
116 Saito S,Ohzono K.Early arteriopathy and postulated pathogenesis of osteonecrosis of femoral head [J].Clin Orthop,1992,277:98.
117Trueta,Harrison.The normal vascular anatomy of the femoral heand in adult man [J].J Bone Joint Surg(Br),1953,35:442.
118胡长根,陈君长,等.激素性股骨头坏死与血液流变学变化的关系[J].西安交通大学学报：医学版,2003,24(6)：597.
119骆生法.激素性股骨头坏死的血液流变学改变[J].浙江中西医结合杂志,2003,13(8)：473.
120张安年,梁民琦,刘元伟,主编.临床常见非合理用药[M].北京：人民卫生出版社,2000,363.
121时光达,陈宝兴,主编.实验骨伤科学[M].北京：人民卫生出版社,152
122赵万军,肖鲁伟,童培建,等.右归饮、鹿马片对激素诱导的兔股骨头坏死的血浆雌二醇、睾酮的影响及疗效观察[J].中医正骨,2000,12(1)：3.
123 Arlets. Ischmia and necrosi of bone. Baltimere 1 london[J]. wiuiams& wilkins,1980:28. 124 Eiji Gotoh; The pathogenesis of femoral Head [M].Clin orthop; 1993 (2927):294-308.
125高根德,周林宽,许林薇,等.中药骨通预防皮质类固醇激素引起的股骨头坏死的实验研究[J].中国中医骨伤科杂志,1992,8(2)：3.
126高根德,周林宽,许林薇,等.骨通、安妥明、维C预防激素性股骨头坏死的实验研究[J].中国骨伤,1992,5(5)：5.
127杜炯,崔明,李明祚,等.诸氏复骨丸治疗激素性股骨头缺血性坏死的组织学实验研究[J].中医正骨,1999,11(8)：5-6.
128崔明,杜炯,李明祚,等.复骨丸防治激素性早期股骨头缺血性坏死血液流变学及脂代谢的实验研究[J].中国中医骨伤科杂志,1999,7(5)：48.
129袁洪,李雄,何伟,等.生脉成骨胶囊预防激素性股骨头缺血性坏死的实验研究[J].中国中医骨伤科杂志,1999,7(4)：4-8.
130洪加源,许书亮,阮景绰.复元散对激素性股骨头微循环影响的实验研究[J].中国骨伤,2001,14(1)：27-28.
131洪加源,康两期,郭林新,等.复元散对激素性股骨头坏死骨内微量元素影响的实验研究[J].中医正骨,2002,14(1)：5-7.
132周景华,王立春.活骨汤治疗股骨头缺血性坏死的实验研究[J].中医药研究,2000,16(1)：45.
133刘日光,沈冯君,杨述华,等.丹仙康骨胶囊对激素性股骨头缺血坏死血运变化的影响[J].中国中医骨伤科杂志,2001,9(5)：15-17.
134齐振熙,曹阳.不同治法对激素性股骨头坏死血液流变学及血脂影响的实验研究[J].中国中医骨伤科杂志,2001,9(5)：30-32.
135王国毓,姚永东,杨毓华,等.骨复生对激素性股骨头缺血坏死家兔血液流变学的影响[J].中医正骨,2001,13(1)：11-12.
136童培建,萧鲁伟,高根德.丹参治疗激素性股骨头无菌性坏死的实验研究[J].浙江医学,1997,19(2)：73.
137张念非,李子荣,杨连发,等实验性股骨头缺血性坏死的药物治疗[J].中日友好医院学报,1997,11(2)：109.
138张晓刚,任远,张剑峰,等.生骨再造散对激素性股骨头坏死模兔血流变学的影响[J].中医正骨,2000,12(10)：3-4.
139徐传毅,黄涛,周季,等从血瘀证论治激素性股骨头坏死的实验研究[J].中国中医骨伤科杂志,2000,8(4)：10-13.
140李毅,赤阳泉,朱超,等.骨复生对激素性股骨头缺血坏死家兔血浆一氧化氮的影响[J].中医正骨,2002,14(7)：8-9.
141李峻辉,宁亚功,彭仲杰,等.中西医结合治疗激素性股骨头坏死的实验研究[J].中国骨伤,2003,16(3)：145-147.
142纪顺心,关雪军,李崇芳.中药续断对大鼠实验性骨损伤愈合作用的观察[J].中草药,1997,28(2)：98—99.
143周铜水,刘晓东,周荣汉.骨碎补对大鼠实验性骨伤愈合的影响[J].中草药,1994,25(5)：249.
144冯伟,傅文或,魏义勇,等.单味中药对成骨相关基因表达的影响[J].中医正骨,2004,16(3)：6—9.
145戴瑞鸿,李勇.冠心病心肌缺血的治疗性血管生成与中医药[J].中国中西医结合杂志2002；203：163—164.
146石清照,罗劲松,夏利平,徐之良,江仲炎.当归注射液影响辐射损伤小鼠骨髓基质细胞血管内皮生长因子及其fit-1的表达受体[J].中国组织工程研究与临床康复2007,11(11)：2100-2103.
147雷燕,高倩,李悦山,陈可冀.黄芪、当归及其组方促血管内皮细胞增殖作用的研究[J].中国中西医结合杂志2003,23(10)：753-756.
1贺西京.激素性股骨头无菌性坏死与摄入激素性剂量的实验研究与临床观察.陕西医学杂志,1990,5：20-23.
2 Cruess RL.The etiology of steroid induced avasculsar necrosis of bone[M].Clin Orthop,1975,113:178-179.
3 Wang GJ.et al.Fat-cell changes as a mechanism of avascula rnecrosis of the femoral head in cortisone-treated rabbits[J] Bone Joint Surg,1977,59A:729.
4 Warner JP.Studies of nontraumatic osteonecrosis[J].J Clin Orthop,1987,225,128-140.
5 Gold EW,et al..Corticosteroid-induced avascular necrosis:An experimental study in rabbits[J]..J Clin Orthop,1978,135:272-274.
6王坤正,毛履真,胡长根,等.激素性股骨头坏死发病机制的实验研究[J].中华外科杂志,1994,32(9)：515-517.
7王心生.激素性股骨头缺血性坏死动物模型的研制[J].中华实验外科杂志,1993,3：136-137.
8.Kawai K.Steroid-induced accumulation of lipid in the osteocytes of the rebbit femoral head[J],1985,67A:755-762.
9Matsui M,Saito S,Ohzono K,et al.Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis[J].Clin Orthop Relat Res,1992,277:61-72.
10李子荣.张念非.岳德波.激素性股骨头缺血性坏死动物模型的诱导和观察[J].中华外科杂志,1995,8：485-487.
11 Yamamoto T.Corticosteroid enhances the experimenta linduction of osteonecrosis in rabbits with Shwartzman reaction [J].JClin Orthop,1995,316,235-243.
12 Jones JP.Fat embolism,intravascular coagulation and osteonecrosis [J]..J Clin Orthop,1993;292:294-308.
13Kenzora JE.Experimental osteonecrosis of the femoral head in adult rabbits[J] J Clin Orthop,1978,130:8.
14李印良,徐莘香,张晓南,等.实验性股骨头坏死血运变化的初步观察[J].骨与关节损伤杂志,1995,10(2)：95-97.
15杨明亮,罗先正,王正明.实验性动物股骨头坏死模型的制备及其病理生理机制[J].中国骨伤,2000；13(4)：207-208.
16王华茂.股骨颈骨折后股骨头缺血性坏死的实验研究[J].J广州医药,1993,4：7.
17刘尚礼.Legg-Perthes病股骨头坏死机理的研究[J].中华外科杂志,1987,11：643-645.
18王义生.酒精性股骨头缺血性坏死发病机理和实验研究.华裔骨科学会第二届学术会议论文汇编,1997,176.
19郭天明,朱天岳.酒精中毒致股骨头坏死的动物模型[J].汕头大学医学院学报,1999,12；12(2)：17-20.
20徐小良,王坤正,闫宏伟,等.实验性股骨头骨缺损修复过程的生物力学研究[J].西安医科大学学报,2001,22(5)：448-450.
21 Calvert PT.Effects of vascular occlusion on the femoral heading rowing rabbits.Acta orthop scand[J],1984,55:526-527.
22许瑞江.机械性压力与股骨头骨骺坏死关系的动物实验研究[J].中华小儿外科杂志,1989,5：288-290.
23.Takaoka K,et al.The repair process in experimentally induced avascular necrosis of the femoral head in dogs [J].Arch OthopTraumat Surg,1981,99:109-115.
24 Malizos KN,Quarles LD,Seaber AV,et al.An experimental canine model of osteonecrosis:characterization of the repair process[J]..J Orthop Res,1993,11(3):350-357.
2张鹤山,李子荣.股骨头坏死诊断与治疗的专家建议[J].中华骨科杂志 2007,27(2)：146-148.
3徐传毅,何伟,李雄.从“瘀血”理论辨识股骨头坏死[J].中国中医基础医学杂志,2002,8(5)：18-19.
4宋剑南.从生物化学角度看痰及痰瘀相关[J].中国中医基础医学杂志,2000,6(3)：40-43.
5刘少军,袁浩.股骨头坏死的中医临床思路与方法探究[J].中国医药学报2002,17(1)：44-47.
6孙材康,娄志强,高建中,等.中医药治疗股骨头缺血性坏死[J].河南中医1996；16(1)：32.
7张铁刚,章艳霞,李敏,等.股骨头坏死中医三型分治的临床总结[J].中国中西医结合外科杂志1998；4(6)：354.
8诸福度,崔明,吴材康,等.股骨头缺血坏死的中医药治疗[J].中国骨伤1994；7(6)：46.
9马素英.马氏骨片治疗股骨头坏死128例X线变化[J].中国骨伤1996；9(4)：23.
10邓沂,张晓刚,任远,等.中医对股骨头坏死的认识[J].甘肃中医学院学报 1998；15(4)：54.
11陈卫衡,刘道兵,张洪美,等.股骨头坏死的三期四型辨证思路[J].中国中医基础医学杂志2003；9(12)：51.
12杜国辉,刘德玉.骨复生对激素性家兔股骨头坏死血清中骨形态发生蛋白-2及转化生长因子-β影响的实验研究[J].陕西中医学院学报2006,29(3).
13刘日光,沈冯君,尹培荣,易诚青.中药对股骨头缺血坏死修复过程中血管内皮生长因子基因表达的影响[J].中国骨伤2004,17(12)：705-707.
14李景田,邹锦慧,张慧明,黄伟,周小璜,李伯灵,陈秀琴.预防用药对激素性股骨头坏死骨细胞凋亡的影响[J].中国临床康复2006,10(27)：168-171.
15田伟明,王文智,王鑫国.骨复活汤对激素性股骨头坏死血液流变学及脂代谢的影响[J].中国中药杂志,2002,27(10)：769～771.
16刘宏泽,王文瑞,卫小春,张剑宇.丹参与骨碎补注射液防治激素诱发股骨头坏死的实验研究[J].中国骨伤2003,16(12)：726-728.
17张弛,杨志伟,朱明双等.活血通络法对激素性股骨头坏死家兔模型的组织形态学影响[J].新医科大学学报2007,30(5)：452-454.
18Miyanishi K,Yamamoto T,Irisa T,Motomura G,Jingushi S,Sueis K,Iwamoto Y.Effects of different corticosteroids on the develoment of osteonecrosis in rabbits[J].J Rheumatology (Oxford) 2004,4(3):332～336.
19陈彦华,殷惠芳,王式鲁.马血清加激素诱导股骨头缺血性坏死动物模型的实验研究[J].山东中医药大学学报,2003,27：222-223.
20刘万林,郭文通,李文琪,等.激素性股骨头缺血性坏死动物模型诱导[J].内蒙古医学院学报,1986；20(2)：71.
21 Mastsui M,Saito S,Ohzoao K,et al.Experimental steroid-induced osteo-necrosis in adult rabbit with hypersensitive vasculitis [J].J Clin orthop.1992,277:61.
22马在山.马氏秘传骨丸治疗股骨头无菌性坏死临床疗效观察[J] 北京中医杂志,1989(1)：48.
23宋剑南,刘东远,牛晓红等.高脂血症与中医痰浊关系的实验研究[J].中国中医基础医学杂志,1995,1：49-50.
24郭宏昌,牛晓亚,张向东.痰浊证与血脂水平关系的研究[J].河南中医药学刊,1998,13(6)：18-19.
25李岩,赵雁,黄启福等.中医络病的现代认识[J].北京中医药大学学报,2002,25(3)：1-5.
26于世凤.骨吸收与骨形成[J].现代康复,2001,5(2)：10..
27苗明三.法定中药药理与临床(第一版)[M].世界图书出版社,1998
28 Lee MH,Kim YJ,Kim HJ,et al. BMP-2-induced runx2 expression is mediated by Dlx5, and TGF-1 Opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression [J]. Biol Chem,2003,278(36):34387-34394.
29 Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM:BMP-2-induced Osterix expression is mediated by DIx5 but is independent of Runx2[J]. Biochem Biophys Res Commun 2003,309:689-694.
30 Choi KY, Kim HJ,Lee MH,et al. Dev Dyn,2005;233(1):115-121
31 Rengachary MD, Bone morphogenetic protein basic connects [J].Neurosurg Focus,2002,13(12):l.
32 Nohe A,Keating E,Underhill T M,et al.Effect of the distribution and clustering of the type I A BMP receptor(ALK3) with the type II BMP receptor on the activationg of signaling path ways[J].J Cell Set 2003,116(pt 16):3277-3284.
33 Sow H,Kaji H,Hendy G N et al.Menin is required for bone morphogenetic protein-2 and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smad and Runx2[J]. J Biol Chem,2004,279(39):40267-40278.
34 Iwasaki S,Iguchi M,Watanabe K,et al.Specific activation of the p38 mitogen-activated protein kinase sigaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2 [J].J Bool Chem,1999,274(37):26503-26510.
35 Lemonnier J, Ghayor C, Guicheux J, et al.Protein kinase C-independent activation of protein kinase D is involved in BMP-2-induced activation of stress mitogen-activated protein kinases JNK and p38 and osteoblastic cell differentiation[J]. J Biol Chem,2004,279(1):259-264.
36 Ohyama Y, Nifuji A, Maeda Y, et al. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis[J]. Endocrinology,2004,145(10):4685-4692.
37 Arikawa T, Omura K, Morita I. Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells[J]. J Cell Physiol,2004,200(3):400-406.
38 Ohyama Y, Nifuji A, Maeda Y, et al. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis [J]. Endocrinology,2004,145(10):4685-4692.
38Cheng H, Jiang W, Phillips F M, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs) [J]. J Bone Joint Surg Am,2003,85-A(8):1544-1552.
40Jorgensen N R, Henriksen Z, Sorensen O H, et al. Dexamethasone,BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype:validation of an in vitro model for human bone marrow-derived primary osteoblasts[J]. Steroids,2004,69 (4):219-226.
41 Osyczka A M, Diefenderfer D L, Bhargave G, et al. Different effects of BMP-2 on marrow stromal cells from human and rat bone[J]. Cells Tissues Organs,2004,176(13):109-119.
42 Dragoo J L, Choi J Y, Lieberman J R, et al. Bone induction by BMP-2 transduced stem cells derived from human fat [J]. J Orthop Res,2003,21(4):622-629.
43 Akita S, Fukui M, Nakagawa H, et al. Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor[J]. Wound Repair Regen,2004,12(2):252-259.
44 Huang W, Carlsen B, Wulur I, et al. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold[J]. Exp Cell Res,2004,299(2):325-334.
45 Huang W, Carlsen B, Wulur I, et al. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two-dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold[J]. Exp Cell Res,2004,299(2):325-334.
46 Bessho K, Carnes D L, Cavin R, et al. Experimental studies on bone induction using low-molecular-weight poly (DL-lactide-co-glycolide)as a carrier for recombinant human bone morphogenetic protein-2[J]. J Biomed Mater Res,2002,61(1):61-65.
47 Woo B H, Fink B F, Page R, et al. Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2in a polymeric matrix[J]. Pharm Res,2001,18(12):1747-1753.
48 Yamamoto M, Takahashi Y, Tabata Y. Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein [J]. Biomaterials,2003,24 (24):4375-4383.
49 Maeda H, Sano A, Fujioka K. Profile of rhBMP-2 release from collagen minipellet and induction of ectopic bone formation[J]. Drug Dev lnd Pharm,2004,30 (5):473-480.
50 Yang X B, Whitaker M J, Sebald W, et al. Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds[J]. Tissue Eng,2004,10(7-8):1037-1045.
51 Okubo Y, Bessho K, Fujimura K, et al. In vitro and in vivo studies of a bone morphogenetie protein-2 expressing adenoviral vector [J]. J Bone Joint Surg Am,2001,83-A Suppl 1 (Pt 2):S99-S104.
52 Xing W, Baylink D, Kesavan C, et al. HSV-1 amplicon-mediated transfer of 128-kb BMP-2 genomic locus stimulates osteobla st differentiation in vitro[J]. Biochem Biophys Res Commun,2004,319 (3):781-786.
53 Prats H, Kaghad M, Prats AC, Klagsbrun M, Lelias JM, Liauzun P et al. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons[J]. J Proc Natl Acad Sci USA, 1989,86:1836-1840.
54 Eriksson AE, Cousens LS, Weaver LH, Matthews BW 1991 Three-dimensional structure of human basic fibroblast growth factor[J]. Proc Natl Acad Sci USA,1991,88:3441-3445.
55 Kiefer MC,Stephans JC,Crawford K,et al.Ligand-affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor [J]. Proc Natl Acad Sci USA,1990,87:69854.
56 Luo Y,Lu W,Mohamedali KA,et al.The glyeine box:a determinant of specificity for fibroblaat growth factor[J].Bio chemistry,1998,37(7):1 6506-15.
57 Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P. Murine FGFR-1 is required for early postimplantation growth and axial organization[J]. Genes Dev.1994; 8:3045-3057.
58 Arman E.Haffner-Krausz R,Chen Y,et al.Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development[J].Proc Natl Acad Sci USA,1998,95(9):5082-5087.
59 Shiang R,Thompson LM,Zhu YZ,et al.Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism,achondroplasia[J].Cell.1994,78:335-342.
60 Peters KG, Marie J,Wilson E,et al.Point mutation an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogeneses [J].Nature,1992,358:678-680.
61 Hadari YR,Kouhara H,Lax I,et al.Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation [J].Mol Cell Biol,1998,18:3966.
62 Xu H,Lee KW,Goldfarb MR.Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins [J].J Biol Chem,1998,273:17987-17989. 63 Weinstein DC,Marden J,Camevali F.FGF-mediated mesoderm induction involves the Src-family kinase Laloo [J].Nature,1998,304:904.
64 Klint P,Kanda S,Kloog Y,et al.Contribution of Src and Ras pathways in FGF-2 induced endothelial cell differentiation [J].Oncogene,1999,18:3354.
65 Brighton CT.Principles of fracture healing.In:cornell CN, Lane JM.Newest factors in fracture healing [J].Clin Orthop,1992,277:297-312.
66 Canalis E,Centrella M,Mccarthy T.Effects of basic fibroblast growth factor on bone formation in vitro[J].J Clin Invest,1988,81:1572-1577.
67 Kotev-Emeth S,Savion N.Effect of maturation on the osterogenic response of cultured stromal bone marrow cells to basic fibroblast growth factor[J].Bone,2000,27(6):777-783.
68 Bolander ME.Regulation of fracture repai rby growth factors [J].Proc Soc Exo Bio Med,1992,200:165-170.
69Niswandr L,Martin G, FGF4 and BMP have opposite effects on limb growth [J].Nature,1993,361:68-71.
70 Seghezzi G,PatelS,Ren CJ,et al.Fibroblast growth factor-2(FGF22) induces vascular endothelial growthfactor(VEGF) expression in the endothelial cells of forming capillaries:anautocrine mechanism contributing to angiogenesis [J].J Cell Biol,1998,141:1659.
71王海彬,何伟,袁浩.成骨细胞和型胶原[J].Chinese Trad Med Traum&Orthop,2003,11(3):56-59.
72 Risau W. Mechanisms of angiogenesis [J].Nature,1997,386(6626):671-674., Carmeliet P. Mechanisms of angiogenesis and arteriogenesis [J]. Nat Med,2000,6(4):389-395.
73 Asahara T, Takahashi T, Masuda H, et al.VEGF contributes to postnatal neovascularization by mobilizing bone marrow-rived endothelial progenitor cells [J]. EMBO J,1999,18 (14):3964-3972.
74 Darland D C, D' more P A. Blood vessel maturation:vascular development comes of age[J]. J Clin Invest,1999, 103(2):157-158.
75 Ohta H, Ishiyama J, Saito H, et al. Effects of pretreatment with basic fibroblast growth factor, epidermal growth factor and nerve growth factor on neuron survival and neovascularization of superior cervical ganglion transplanted into the third ventricle in rats[J]. Jpn J Pharmacol,1991,55(2):255-262.
76 Galiano R D, Tepper O M, Pelo C R, et al.Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells[J]. Am J Pathol,2004,164(6):1935-1947.
77 Soker S. Neuropilin in the midst of cell migration and retraction[J].Int J Biochem Cell Biol,2001,33(4):433-437.
78 Veikkola T, Alitalo K. VEGFs receptors and angiogenesis[J]. Semin Cancer Biol,1999,9(3):211-220.
79 Soker S, Takashima S, Miao H Q, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor[J]. Cell,1998,92(6):735-745.
80 Eckardt H, Bundgaard K G, Christensen K S, et al. Effects oflocally applied vascular endothelial growth factor (VEGF) and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis [J]. J Orthop Res,2003,21(2): 335-340:
81 Gu F, Amsden B, Neufeld R. Sustained delivery of vascular endothelial growth factor with alginate beads[J] J Control Release,2004,96 (3):463-472.
82 Murphy W L, Peters M C, Kohn D H, et al. Sustained release of vascular endothelial growth factor from mineralized poly (lactide-co-glycolide) scaffolds for tissue engineering[J]. Biomaterials,2000,21(24):2521-2527.
83 Murphy W L, Simmons C A, Kaigler D, et al. Bone regeneration via a mineral substrate and induced angiogenesis[J]. J Dent Res,2004,83(3):204-210.
84 Richardson T P, Peters M C, Ennett A B, et al. Polymeric system for dual growth factor delivery[J]. Nat Biotechnol,2001,19 (11):1029-1034.
85 Zisch A H, Lutolf M P, Ehrbar M, et al.Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth[J]. FASEB J,2003,17 (15):2260-2262.
86 Soker S, Machado M, Atala A. Systems for therapeutic angiogenesis in tissue engineering[J]. World J Urol, 2000,18(1):10-18.
87 Wu X, Rabkin Aikawa E, Guleserian K J, et al.Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells[J]. Am J Physiol Heart Circ Physiol,2004,287 (2):H480-H487.
88 Wijelath E S, Rahman S, Murray J, et al.Fibronectin promotes VEGF-induced CD34 cell differentiation into endothelial cells[J]. J Vasc Surg,2004,39 (3):655-660.
89 Kubo K, Kuroyanagi Y. Characterization of a cultured dermal substitute composed of a spongy matrix of hyaluronic acid and collagen combined with fibroblasts[J]. J Artif Organs,2003,6(2):138-144.
90Kaigler D, Krebsbach P H, Polverini P J, et al. Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells[J]. Tissue Eng,2003,9 (1):95-103.
91 Street J, Bao M, deGuzman L, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover[J]. Proc Natl Acad Sci U S A,2002,99(15):9656-9661.
92 Chang CS, Su CY, Lin TC. Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts[J]. J Biomed Mater Res,1999,48(4):411-416.
93 Lu Y, Shansky J, Del Tatto M, et al. Recombinant vascular endothelial growth factor secreted from tissue-engineered bioartificial muscles promotes localized angiogenesis[J]. Circulation,2001,104 (5):594-599.
94Thompson CB.Apoptosis in the pathogenesis and treatment of disease [J].Science,1995,267:1456-1462.
95 Tsujimoto Y,Cossman J,Jaffe E,et al. Involvement of the bcl-2 gene in human follicular lymphoma[J].Science,1985,228:1440-1443.
96Reed JC.Mechanisms of apoptosis[J].Am JPathol,2000,157:1415-1430.
97Adams JM,Cory S.The Bcl-2 protein family:arbiters of cell survival[J].Science,1998,281:1322-1326.
98Green DR,Reed JC.Mitochondria and apoptosis [J].Science,1998,2811309-1312.
99Wolter KG,Hsu YT,Smith CL,et al.Movement of Bax from the cytosol to mitochondria during apoptosis[J].J Cell Biol,1997,139:1281-1292.
100 Oltvai ZN,Milliman CL,Korsmeyer SJ.Bcl-2 heterodimerizes in vivo with a conserved homolog,Bax,that accelerates programmed cell death[J]. Cell,1993,74:609-619.
101 Sato T,Hanada M,Bodrug S,et al.Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system[J].Proc Natl Acad Sci USA,1994,91:9238-9242.
102Muchmore SW,Sattler M,Liang H,et al.Links X-ray and NMR structure of human Bcl-XL,aninhibitor of programmed cell death[J].Nature,1996,381:335-341.
103李楠,王和鸣.体外培养成骨细胞研究新进展[J].中国骨伤,2003,16(3)：187-189.
104Edward PJ.Osteotoxicology:the role of lead in bone diseases[J]. Curr Opin Orthop,2000,11(5):360-365.
105Sato M,et al.Apoptosis and expression of stress protein during development of ischaemic osteonecrosis in the rat [J]. J Bone Joint Surg Br 2001,83(5):751-759.
106胡野,凌志强,单小云主编.细胞凋亡的分子医学[M].北京军事医学科学出版社,2002.62-70.
107李靖,王权平,张颖.Bcl-2 过表达对 TNF2A 诱导大鼠成骨细胞凋亡的影响[J].中国骨质疏松杂志,2003,9(4)：295-298.
108何伟,方斌,庞智辉,等.激素性股骨头坏死的早中期超微结构观察[J].中医正骨,2000,12(7)：4.
109贺西京,毛履真,王坤正,等.肾上腺皮质激素引起股骨头缺血性坏死的机制实验研究[J].中华骨科杂志,1992,12(6)：440.
110贺西京,毛履真,王坤正,等.激素性股骨头坏死与骨细胞脂肪变性的实验研究[J].中华骨科杂志,1996,16(1)：45.
111孙强,施裕新,等.激素性股骨头坏死发病机制的实验研究[J].中国临床医学,2003,10(4)：465.
112 Jines JP.Intravascular coagulation and osteonecrosisc [J].Clin Orthop,1992,277:41.
113袁浩,李雄,何伟,等.生脉成骨胶囊预防激素性股骨头缺血性坏死的实验研究[J].中国中医骨伤,1999,7(4)：4-8.
114赵万军,肖鲁伟,董培建.激素诱导股骨头缺血性坏死的发病机理及中医药的防治[J].中国中医骨伤科杂志,1998,6(3)：50.
115Starklink H,Lausten GS,Amoldi CC.Microvascular obstruction invascular necrosis,immunohistochmistry of 14 femoral headc[J].Acta Orthop Scand,1995,66:9.
116 Saito S,Ohzono K.Early arteriopathy and postulated pathogenesis of osteonecrosis of femoral head [J].Clin Orthop,1992,277:98.
117Trueta,Harrison.The normal vascular anatomy of the femoral heand in adult man [J].J Bone Joint Surg(Br),1953,35:442.
118胡长根,陈君长,等.激素性股骨头坏死与血液流变学变化的关系[J].西安交通大学学报：医学版,2003,24(6)：597.
119骆生法.激素性股骨头坏死的血液流变学改变[J].浙江中西医结合杂志,2003,13(8)：473.
120张安年,梁民琦,刘元伟,主编.临床常见非合理用药[M].北京：人民卫生出版社,2000,363.
121时光达,陈宝兴,主编.实验骨伤科学[M].北京：人民卫生出版社,152
122赵万军,肖鲁伟,童培建,等.右归饮、鹿马片对激素诱导的兔股骨头坏死的血浆雌二醇、睾酮的影响及疗效观察[J].中医正骨,2000,12(1)：3.
123 Arlets. Ischmia and necrosi of bone. Baltimere 1 london[J]. wiuiams& wilkins,1980:28. 124 Eiji Gotoh; The pathogenesis of femoral Head [M].Clin orthop; 1993 (2927):294-308.
125高根德,周林宽,许林薇,等.中药骨通预防皮质类固醇激素引起的股骨头坏死的实验研究[J].中国中医骨伤科杂志,1992,8(2)：3.
126高根德,周林宽,许林薇,等.骨通、安妥明、维C预防激素性股骨头坏死的实验研究[J].中国骨伤,1992,5(5)：5.
127杜炯,崔明,李明祚,等.诸氏复骨丸治疗激素性股骨头缺血性坏死的组织学实验研究[J].中医正骨,1999,11(8)：5-6.
128崔明,杜炯,李明祚,等.复骨丸防治激素性早期股骨头缺血性坏死血液流变学及脂代谢的实验研究[J].中国中医骨伤科杂志,1999,7(5)：48.
129袁洪,李雄,何伟,等.生脉成骨胶囊预防激素性股骨头缺血性坏死的实验研究[J].中国中医骨伤科杂志,1999,7(4)：4-8.
130洪加源,许书亮,阮景绰.复元散对激素性股骨头微循环影响的实验研究[J].中国骨伤,2001,14(1)：27-28.
131洪加源,康两期,郭林新,等.复元散对激素性股骨头坏死骨内微量元素影响的实验研究[J].中医正骨,2002,14(1)：5-7.
132周景华,王立春.活骨汤治疗股骨头缺血性坏死的实验研究[J].中医药研究,2000,16(1)：45.
133刘日光,沈冯君,杨述华,等.丹仙康骨胶囊对激素性股骨头缺血坏死血运变化的影响[J].中国中医骨伤科杂志,2001,9(5)：15-17.
134齐振熙,曹阳.不同治法对激素性股骨头坏死血液流变学及血脂影响的实验研究[J].中国中医骨伤科杂志,2001,9(5)：30-32.
135王国毓,姚永东,杨毓华,等.骨复生对激素性股骨头缺血坏死家兔血液流变学的影响[J].中医正骨,2001,13(1)：11-12.
136童培建,萧鲁伟,高根德.丹参治疗激素性股骨头无菌性坏死的实验研究[J].浙江医学,1997,19(2)：73.
137张念非,李子荣,杨连发,等实验性股骨头缺血性坏死的药物治疗[J].中日友好医院学报,1997,11(2)：109.
138张晓刚,任远,张剑峰,等.生骨再造散对激素性股骨头坏死模兔血流变学的影响[J].中医正骨,2000,12(10)：3-4.
139徐传毅,黄涛,周季,等从血瘀证论治激素性股骨头坏死的实验研究[J].中国中医骨伤科杂志,2000,8(4)：10-13.
140李毅,赤阳泉,朱超,等.骨复生对激素性股骨头缺血坏死家兔血浆一氧化氮的影响[J].中医正骨,2002,14(7)：8-9.
141李峻辉,宁亚功,彭仲杰,等.中西医结合治疗激素性股骨头坏死的实验研究[J].中国骨伤,2003,16(3)：145-147.
142纪顺心,关雪军,李崇芳.中药续断对大鼠实验性骨损伤愈合作用的观察[J].中草药,1997,28(2)：98—99.
143周铜水,刘晓东,周荣汉.骨碎补对大鼠实验性骨伤愈合的影响[J].中草药,1994,25(5)：249.
144冯伟,傅文或,魏义勇,等.单味中药对成骨相关基因表达的影响[J].中医正骨,2004,16(3)：6—9.
145戴瑞鸿,李勇.冠心病心肌缺血的治疗性血管生成与中医药[J].中国中西医结合杂志2002；203：163—164.
146石清照,罗劲松,夏利平,徐之良,江仲炎.当归注射液影响辐射损伤小鼠骨髓基质细胞血管内皮生长因子及其fit-1的表达受体[J].中国组织工程研究与临床康复2007,11(11)：2100-2103.
147雷燕,高倩,李悦山,陈可冀.黄芪、当归及其组方促血管内皮细胞增殖作用的研究[J].中国中西医结合杂志2003,23(10)：753-756.
1贺西京.激素性股骨头无菌性坏死与摄入激素性剂量的实验研究与临床观察.陕西医学杂志,1990,5：20-23.
2 Cruess RL.The etiology of steroid induced avasculsar necrosis of bone[M].Clin Orthop,1975,113:178-179.
3 Wang GJ.et al.Fat-cell changes as a mechanism of avascula rnecrosis of the femoral head in cortisone-treated rabbits[J] Bone Joint Surg,1977,59A:729.
4 Warner JP.Studies of nontraumatic osteonecrosis[J].J Clin Orthop,1987,225,128-140.
5 Gold EW,et al..Corticosteroid-induced avascular necrosis:An experimental study in rabbits[J]..J Clin Orthop,1978,135:272-274.
6王坤正,毛履真,胡长根,等.激素性股骨头坏死发病机制的实验研究[J].中华外科杂志,1994,32(9)：515-517.
7王心生.激素性股骨头缺血性坏死动物模型的研制[J].中华实验外科杂志,1993,3：136-137.
8.Kawai K.Steroid-induced accumulation of lipid in the osteocytes of the rebbit femoral head[J],1985,67A:755-762.
9Matsui M,Saito S,Ohzono K,et al.Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis[J].Clin Orthop Relat Res,1992,277:61-72.
10李子荣.张念非.岳德波.激素性股骨头缺血性坏死动物模型的诱导和观察[J].中华外科杂志,1995,8：485-487.
11 Yamamoto T.Corticosteroid enhances the experimenta linduction of osteonecrosis in rabbits with Shwartzman reaction [J].JClin Orthop,1995,316,235-243.
12 Jones JP.Fat embolism,intravascular coagulation and osteonecrosis [J]..J Clin Orthop,1993;292:294-308.
13Kenzora JE.Experimental osteonecrosis of the femoral head in adult rabbits[J] J Clin Orthop,1978,130:8.
14李印良,徐莘香,张晓南,等.实验性股骨头坏死血运变化的初步观察[J].骨与关节损伤杂志,1995,10(2)：95-97.
15杨明亮,罗先正,王正明.实验性动物股骨头坏死模型的制备及其病理生理机制[J].中国骨伤,2000；13(4)：207-208.
16王华茂.股骨颈骨折后股骨头缺血性坏死的实验研究[J].J广州医药,1993,4：7.
17刘尚礼.Legg-Perthes病股骨头坏死机理的研究[J].中华外科杂志,1987,11：643-645.
18王义生.酒精性股骨头缺血性坏死发病机理和实验研究.华裔骨科学会第二届学术会议论文汇编,1997,176.
19郭天明,朱天岳.酒精中毒致股骨头坏死的动物模型[J].汕头大学医学院学报,1999,12；12(2)：17-20.
20徐小良,王坤正,闫宏伟,等.实验性股骨头骨缺损修复过程的生物力学研究[J].西安医科大学学报,2001,22(5)：448-450.
21 Calvert PT.Effects of vascular occlusion on the femoral heading rowing rabbits.Acta orthop scand[J],1984,55:526-527.
22许瑞江.机械性压力与股骨头骨骺坏死关系的动物实验研究[J].中华小儿外科杂志,1989,5：288-290.
23.Takaoka K,et al.The repair process in experimentally induced avascular necrosis of the femoral head in dogs [J].Arch OthopTraumat Surg,1981,99:109-115.
24 Malizos KN,Quarles LD,Seaber AV,et al.An experimental canine model of osteonecrosis:characterization of the repair process[J]..J Orthop Res,1993,11(3):350-357.