国新牌骨痛膏促进家兔骨愈合的实验研究
摘要
研究背景
骨折是骨科临床的常见病和多发病,随着社会经济的发展,交通运输高度发达,而且中国逐渐迈入老龄化社会,骨折成高发态势。据统计约有5%-10%的骨折可因各种原因发生骨折迟缓性愈合及不愈合。目前,国外对于药物促进骨折愈合的研究较少,国内的研究也多侧重于中药内服,相对中药内服促进骨愈合而言,外用中药促进骨愈合的研究水平不高。中医药治疗骨折已有漫长的历史,经验丰富。1931年出土的《居延汉简》中就记录了汉代军医以膏药为主治疗各种创伤的方药和方法,可见早在秦汉时代应用敷贴治疗骨伤就已经很普遍了。因此利用现代分子生物学及细胞生物学深入研究并揭示外用中药治疗骨折的疗效及机制有重要的现实意义和社会意义。国新牌骨痛膏源自吉林省民间验方,为促进骨愈合的一种外用膏剂,在临床应用多年,疗效确切,治愈大量骨折、骨不连、骨坏死病人,但是作用机制仍不清楚,本研究拟通过检测血生化指标、X线评分、组织切片观察、胶原分型、骨形态发生蛋白(BMP-2)免疫组化、骨形态发生蛋白(BMP-2)原位杂交等方法验证其促进促进骨愈合的效果,从现代医学的角度探讨其促进骨愈合的的作用机制,进而从现代医学角度为外用中药促进骨愈合提供更为科学的依据。
研究目的
探讨国新牌骨痛膏促骨愈合效果,揭示其促进骨愈合的可能机理。
研究方法
将30只日本大耳白兔均以手术造成双桡骨中段宽约3mm、深达髓腔的骨缺损模型,术后观察日本大白兔的一般情况。再将造模成功的30只日本大耳白兔随机分成国新牌骨痛膏外用药组和空白对照组,再将每组15只随机分成三个亚组,即第1周取标本组(A组)、第2周取标本组(B组)、第4周取标本组(C组),空白对照组以石膏固定,给药组外敷国新牌骨痛膏后以石膏固定,给药组每2天换一次药,1周处死A组,2周处死B组,4周处死C组。每组处死前均予耳缘静脉取血,检测血中ALP、钙、磷、镁浓度,两组行t检验；处死后拍摄双侧桡骨侧位X光片肉眼观察评分,A、B、C各组行t检验比较；病理学HE、Masson染色观察；Ⅰ、Ⅲ型胶原苦味天狼星染色后偏正光显微镜观察分析；免疫组化法检测桡骨缺损处骨形态发生蛋白(Bone Morphogenetic Protein, BMP-2)的表达,测MOD值后A、B、C各组行t检验；原位杂交法检测桡骨缺损处骨形态发生蛋白(Bone Morphogenetic Protein, BMP-2)的表达,测MOD值后A、B、C各组行t检验。
研究结果
术后各组实验兔的一般情况良好；术后1、2、4周时,生化指标检查：给药组与对照组血中ALP、钙、磷、镁及钙磷乘积值均无统计学差异；放射学检查：术后第1周给药组即有骨痂形成,对照组未见骨痂生长。术后第2周两组均可见骨痂形成,给药组骨折缺损区有较完全的骨痂填满并见大量外骨痂形成,对照组骨折缺损区可见软性骨痂填充,大部分无外骨痂。术后第4周给药组缺损区骨皮质重建,骨干外形恢复,髓腔再通,对照组缺损区骨痂基本填满,仍有连接性骨痂阴影,髓腔未通。各组X线片肉眼观察评分结果给药组的得分均高于空白对照组,统计学差异显著；病理学HE、Masson染色观察发现给药组第1周即出现骨痂,第2周外骨痂明显,第4周缺损部位骨痂中胶原明显减少,骨缺损修复质量好。对照组第1周时未见骨痂形成,第2周大部分无外骨痂,第4周缺损部位骨痂仍含有大量胶原,修复质量较给药组差；Ⅱ、Ⅲ型胶原苦味天狼星染色结果,给药组的Ⅰ型胶原出现较对照组早,且Ⅰ型胶原含量高；BMP-2免疫组化及原位杂交结果给药组BMP-2mRNA的表达出现时间早于对照组,表达程度明显优于对照组,统计学差异显著。
结论
(1)国新牌骨痛膏对血ALP、钙、磷、镁及钙磷乘积没有影响。
(2)国新牌骨痛膏可以促进Ⅰ型胶原的表达。
(3)国新牌骨痛膏可以调节BMP-2的合成、分泌并促进BMP-2的表达
(4)国新牌骨痛膏可以使骨痂提前出现,提高骨愈合质量,缩短愈合时间,促进骨愈合
Study background
Fracture is the common disease in the clinical practice. Along with social economy's development, the transportation is highly developed, moreover China enters into the aging society gradually, the fracture becomes more frequently. Statistically, there is approximate 5%-10% fractures may lead to the slow cicatrization and disunion by each kind of reason. At present, there are few research about promoting healing by medicine overseas. The domestic research also stresses on the oral administration of traditional Chinese medicine, the level of research about traditional Chinese medicine external using promoting healing is not high compared to the oral administration. The history is long in Fracture treated with the Chinese medicine, and also has the rich experience. "Occupied Extends Chinese Jan" unearthed in 1931 had recorded the medicine external use which could treat wound by military doctor in Han Dynasty. Obviously it is very common as early as in the Qin and Han Dynasty. Therefore, curative effect and the mechanism of the external use of traditional Chinese medicine through modern molecular biology and cytobiology has the vital practical significance and the social meaning."Guoxin ostalgia ointment" is a folk recipe and comes from Jilin Province. It is a kind of external use medicinal and can promote fracture healing. It has been many years in clinical practice and has the excellent curative effect.“Guoxin ostalgia ointment”had cured massive patient with bone fractures, the bone do not link and the osteonecrosis. But the mechanism is not clear yet, through testing biochemical indicator, X ray grading, tissue slice analysis, the collagen typing, immunohistochemistry test of the bone morphogenesis protein (BMP-2) and hybridization in situ test for bone morphogenesis protein (BMP-2), author hopes to reveal the mechanism of promoting fracture healing and also hopes to provide more scientific evidence for external use of traditional Chinese medicine from the view of modern medicine.
Study objective
To study the therapy effect of "Guoxin ostalgia ointment" and to reveal the possible mechanism of promoting fracture healing.
Study methods
Fracture models were made by operation.3mm bone defect was made on the middle shafts of both Japanese rabbits in each bone. Observe the post-operation general conditions of the Japanese rabbits. Thirty rabbits were randomly assigned to receive "Guoxin ostalgia ointment" and blank control groups.15 rabbits in each of the two groups. Then each group were assigned to 3 sub-groups. With specimen collection from rabbits postoperative 1 week (A),2 week (B) and 4 week(C).All of the experimental rabbits were made to the bone defect model with 3mm wide to the pulp chamber located on the midpiece of bi-radial. Rabbits in blank control group were received by gypsum exclusively. Rabbits in experimental group were received by"Guoxin ostalgia ointment" external use add gypsum fixation. Experimental group changed addressing per two days. Execute the rabbits in A sub-group after first week. Execute the rabbits in B sub-group after second week. Execute the rabbits in C sub-group after fourth week. Test ALP, Calcium, Phosphorus and Magnesium from blood of ear vein. Shot the bi-radial X ray film. T-test was used to statistic the three group(A,B,C). Pathology test by the method of HE, Masson dyeing. light microscope observation ofⅠ,Ⅲcollagen bitter taste sirius dyeing. BMP-2 was tested by the method of immunohistochemistry and hybridization in situ. T test was applied to the A,B,C each group after testing the value of MOD.
Study results
Each group of rabbit's general conditions is good. Biochemical indicator of 1,2,4 week after operation showed:There is no difference between experimental group and blank control group on the effect of blood density of ALP, Calcium, Phosphorus, Magnesium and calcium-phosphorus product. The result of postoperative 1st week showed:"Guoxin ostalgia ointment" can enhance the BMP-2 expression and bony callus formulation; Reduce healing time. Callus formation was occurred by the radiological examination and there is no bony callus in the blank control group. The result of postoperative 2nd week showed:There exist bony callus in both two group. Bony callus stuffed the bone defect area and massive external callus formation appeared in the experimental group. And there is no external callus but soft callus stuff in the blank group. The result of postoperative 4th week showed:medicine group's bone cerebral cortex reconstruction was appeared in the damage area, the backbone contour restored, the medulla cavity passed again. And callus filled up basically in the control group damage area, connective callus shadow still existed, the medulla cavity had not pass. Through macroscopic observation of X ray, the store of medicine group is higher than the control group and there is obvious difference in statistics. Through the HE and Masson dyeing, in the 1st week, there appeared bony callus in the medication group and there existed obvious bony callus in the 2nd week. In the 4th week, the collagen reduction was obvious in the defect area and the quality was good; In the control group, callus formed in the 1st week, there did not have the external callus in the 2nd week, there existed massive collagens in the 4th week in the damage area and the requirement quality was worse than the experimental group.Ⅰ,Ⅲcollagen bitter taste sirius dyeing result:experimental group appeared earlier than the control group and had more I collagen; BMP-2 was tested by the method of immunohistochemistry and hybridization and the result indicated that the experimental group appeared earlier than the control group, the expressive degree was obvious outweigh the control group and there was obvious difference in statistic.
Conclusion
(1) "Guoxin ostalgia ointment" doesn't affect the ALP, Calcium, Phosphorus, Magnesium and calcium-phosphorus product.
(2) "Guoxin ostalgia ointment" can enhance the expression of I type collagen.
(3)“Guoxin ostalgia ointment”can regulate the formulation、externalization and promote the BMP-2 expression.
(4) "Guoxin ostalgia ointment" can make the bony callus appears earlier, improve the bone healing quality, reduce the healing time and promote the healing progress.
骨折是骨科临床的常见病和多发病,随着社会经济的发展,交通运输高度发达,而且中国逐渐迈入老龄化社会,骨折成高发态势。据统计约有5%-10%的骨折可因各种原因发生骨折迟缓性愈合及不愈合。目前,国外对于药物促进骨折愈合的研究较少,国内的研究也多侧重于中药内服,相对中药内服促进骨愈合而言,外用中药促进骨愈合的研究水平不高。中医药治疗骨折已有漫长的历史,经验丰富。1931年出土的《居延汉简》中就记录了汉代军医以膏药为主治疗各种创伤的方药和方法,可见早在秦汉时代应用敷贴治疗骨伤就已经很普遍了。因此利用现代分子生物学及细胞生物学深入研究并揭示外用中药治疗骨折的疗效及机制有重要的现实意义和社会意义。国新牌骨痛膏源自吉林省民间验方,为促进骨愈合的一种外用膏剂,在临床应用多年,疗效确切,治愈大量骨折、骨不连、骨坏死病人,但是作用机制仍不清楚,本研究拟通过检测血生化指标、X线评分、组织切片观察、胶原分型、骨形态发生蛋白(BMP-2)免疫组化、骨形态发生蛋白(BMP-2)原位杂交等方法验证其促进促进骨愈合的效果,从现代医学的角度探讨其促进骨愈合的的作用机制,进而从现代医学角度为外用中药促进骨愈合提供更为科学的依据。
研究目的
探讨国新牌骨痛膏促骨愈合效果,揭示其促进骨愈合的可能机理。
研究方法
将30只日本大耳白兔均以手术造成双桡骨中段宽约3mm、深达髓腔的骨缺损模型,术后观察日本大白兔的一般情况。再将造模成功的30只日本大耳白兔随机分成国新牌骨痛膏外用药组和空白对照组,再将每组15只随机分成三个亚组,即第1周取标本组(A组)、第2周取标本组(B组)、第4周取标本组(C组),空白对照组以石膏固定,给药组外敷国新牌骨痛膏后以石膏固定,给药组每2天换一次药,1周处死A组,2周处死B组,4周处死C组。每组处死前均予耳缘静脉取血,检测血中ALP、钙、磷、镁浓度,两组行t检验；处死后拍摄双侧桡骨侧位X光片肉眼观察评分,A、B、C各组行t检验比较；病理学HE、Masson染色观察；Ⅰ、Ⅲ型胶原苦味天狼星染色后偏正光显微镜观察分析；免疫组化法检测桡骨缺损处骨形态发生蛋白(Bone Morphogenetic Protein, BMP-2)的表达,测MOD值后A、B、C各组行t检验；原位杂交法检测桡骨缺损处骨形态发生蛋白(Bone Morphogenetic Protein, BMP-2)的表达,测MOD值后A、B、C各组行t检验。
研究结果
术后各组实验兔的一般情况良好；术后1、2、4周时,生化指标检查：给药组与对照组血中ALP、钙、磷、镁及钙磷乘积值均无统计学差异；放射学检查：术后第1周给药组即有骨痂形成,对照组未见骨痂生长。术后第2周两组均可见骨痂形成,给药组骨折缺损区有较完全的骨痂填满并见大量外骨痂形成,对照组骨折缺损区可见软性骨痂填充,大部分无外骨痂。术后第4周给药组缺损区骨皮质重建,骨干外形恢复,髓腔再通,对照组缺损区骨痂基本填满,仍有连接性骨痂阴影,髓腔未通。各组X线片肉眼观察评分结果给药组的得分均高于空白对照组,统计学差异显著；病理学HE、Masson染色观察发现给药组第1周即出现骨痂,第2周外骨痂明显,第4周缺损部位骨痂中胶原明显减少,骨缺损修复质量好。对照组第1周时未见骨痂形成,第2周大部分无外骨痂,第4周缺损部位骨痂仍含有大量胶原,修复质量较给药组差；Ⅱ、Ⅲ型胶原苦味天狼星染色结果,给药组的Ⅰ型胶原出现较对照组早,且Ⅰ型胶原含量高；BMP-2免疫组化及原位杂交结果给药组BMP-2mRNA的表达出现时间早于对照组,表达程度明显优于对照组,统计学差异显著。
结论
(1)国新牌骨痛膏对血ALP、钙、磷、镁及钙磷乘积没有影响。
(2)国新牌骨痛膏可以促进Ⅰ型胶原的表达。
(3)国新牌骨痛膏可以调节BMP-2的合成、分泌并促进BMP-2的表达
(4)国新牌骨痛膏可以使骨痂提前出现,提高骨愈合质量,缩短愈合时间,促进骨愈合
Study background
Fracture is the common disease in the clinical practice. Along with social economy's development, the transportation is highly developed, moreover China enters into the aging society gradually, the fracture becomes more frequently. Statistically, there is approximate 5%-10% fractures may lead to the slow cicatrization and disunion by each kind of reason. At present, there are few research about promoting healing by medicine overseas. The domestic research also stresses on the oral administration of traditional Chinese medicine, the level of research about traditional Chinese medicine external using promoting healing is not high compared to the oral administration. The history is long in Fracture treated with the Chinese medicine, and also has the rich experience. "Occupied Extends Chinese Jan" unearthed in 1931 had recorded the medicine external use which could treat wound by military doctor in Han Dynasty. Obviously it is very common as early as in the Qin and Han Dynasty. Therefore, curative effect and the mechanism of the external use of traditional Chinese medicine through modern molecular biology and cytobiology has the vital practical significance and the social meaning."Guoxin ostalgia ointment" is a folk recipe and comes from Jilin Province. It is a kind of external use medicinal and can promote fracture healing. It has been many years in clinical practice and has the excellent curative effect.“Guoxin ostalgia ointment”had cured massive patient with bone fractures, the bone do not link and the osteonecrosis. But the mechanism is not clear yet, through testing biochemical indicator, X ray grading, tissue slice analysis, the collagen typing, immunohistochemistry test of the bone morphogenesis protein (BMP-2) and hybridization in situ test for bone morphogenesis protein (BMP-2), author hopes to reveal the mechanism of promoting fracture healing and also hopes to provide more scientific evidence for external use of traditional Chinese medicine from the view of modern medicine.
Study objective
To study the therapy effect of "Guoxin ostalgia ointment" and to reveal the possible mechanism of promoting fracture healing.
Study methods
Fracture models were made by operation.3mm bone defect was made on the middle shafts of both Japanese rabbits in each bone. Observe the post-operation general conditions of the Japanese rabbits. Thirty rabbits were randomly assigned to receive "Guoxin ostalgia ointment" and blank control groups.15 rabbits in each of the two groups. Then each group were assigned to 3 sub-groups. With specimen collection from rabbits postoperative 1 week (A),2 week (B) and 4 week(C).All of the experimental rabbits were made to the bone defect model with 3mm wide to the pulp chamber located on the midpiece of bi-radial. Rabbits in blank control group were received by gypsum exclusively. Rabbits in experimental group were received by"Guoxin ostalgia ointment" external use add gypsum fixation. Experimental group changed addressing per two days. Execute the rabbits in A sub-group after first week. Execute the rabbits in B sub-group after second week. Execute the rabbits in C sub-group after fourth week. Test ALP, Calcium, Phosphorus and Magnesium from blood of ear vein. Shot the bi-radial X ray film. T-test was used to statistic the three group(A,B,C). Pathology test by the method of HE, Masson dyeing. light microscope observation ofⅠ,Ⅲcollagen bitter taste sirius dyeing. BMP-2 was tested by the method of immunohistochemistry and hybridization in situ. T test was applied to the A,B,C each group after testing the value of MOD.
Study results
Each group of rabbit's general conditions is good. Biochemical indicator of 1,2,4 week after operation showed:There is no difference between experimental group and blank control group on the effect of blood density of ALP, Calcium, Phosphorus, Magnesium and calcium-phosphorus product. The result of postoperative 1st week showed:"Guoxin ostalgia ointment" can enhance the BMP-2 expression and bony callus formulation; Reduce healing time. Callus formation was occurred by the radiological examination and there is no bony callus in the blank control group. The result of postoperative 2nd week showed:There exist bony callus in both two group. Bony callus stuffed the bone defect area and massive external callus formation appeared in the experimental group. And there is no external callus but soft callus stuff in the blank group. The result of postoperative 4th week showed:medicine group's bone cerebral cortex reconstruction was appeared in the damage area, the backbone contour restored, the medulla cavity passed again. And callus filled up basically in the control group damage area, connective callus shadow still existed, the medulla cavity had not pass. Through macroscopic observation of X ray, the store of medicine group is higher than the control group and there is obvious difference in statistics. Through the HE and Masson dyeing, in the 1st week, there appeared bony callus in the medication group and there existed obvious bony callus in the 2nd week. In the 4th week, the collagen reduction was obvious in the defect area and the quality was good; In the control group, callus formed in the 1st week, there did not have the external callus in the 2nd week, there existed massive collagens in the 4th week in the damage area and the requirement quality was worse than the experimental group.Ⅰ,Ⅲcollagen bitter taste sirius dyeing result:experimental group appeared earlier than the control group and had more I collagen; BMP-2 was tested by the method of immunohistochemistry and hybridization and the result indicated that the experimental group appeared earlier than the control group, the expressive degree was obvious outweigh the control group and there was obvious difference in statistic.
Conclusion
(1) "Guoxin ostalgia ointment" doesn't affect the ALP, Calcium, Phosphorus, Magnesium and calcium-phosphorus product.
(2) "Guoxin ostalgia ointment" can enhance the expression of I type collagen.
(3)“Guoxin ostalgia ointment”can regulate the formulation、externalization and promote the BMP-2 expression.
(4) "Guoxin ostalgia ointment" can make the bony callus appears earlier, improve the bone healing quality, reduce the healing time and promote the healing progress.
引文
[1]周雪明,朱文雄.葛根素对骨折后骨和骨骼肌血流的影响[J].中国热带医学,2005,5(5)：1067～1068.
[2]叶维建,郑玉涛.活血散促进骨折愈合的试验研究[J].牡丹江医学院学报,2005,26(5)：23～25.
[3]李光辉,陈超.伤科接骨片对家兔骨折后血液流变性的影响[J].中国中医急症,2003,12(1)：61.
[4]赵志强,王体沛,王俊芳.丹参与川芎嗪对家兔骨折后血液流变学的影响[J].华中医学杂志,2005,29(5)：374～375.
[5]张志敬,周辉,赵万军,等.和胃接骨胶囊促进试验性骨折的超微结构观察[J].中国中医骨伤科杂志2007,15(3)：26～29.
[6]陈玲,杨云洲,陈继革.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[7]张金海,张伟成.补肾活血合剂促进骨折愈合的实验研究[J].现代中西医结合杂志,2007,16(10)：1321～1322.
[8]罗佩强.土鳖虫促进骨折愈合的实验研究[J].中国骨伤,1992,5(6)：61.
[9]阮朝阳,祁开泽.中药促进骨折愈合作用机制的实验研究进展[J].湖南中医药导报,2003,9(2)：48～49.
[10]高越,胡海翔.复合中药制剂促进大鼠骨折愈合的实验研究[J].科学技术与工程,：2007,7(6)：1164～1166.
[11]董华,胡乃武,董清平.骨痛仙胶囊对家兔骨折血清碱性磷酸酶、钙、磷影响的实验研究[J].中医药学报,2003,31(2)：51～52.
[12]冯坤,陈宝龙,王健智,等.益生接骨颗粒对肾虚骨折家兔骨痂骨矿成分的影响[J].中国中医骨伤科杂志,2005,13(1)：1-4.
[13]谢艳,朱太咏,毕军花,等.益气生骨颗粒对大鼠骨折愈合骨痂中无机质及钙含量的影响[J].中国组织工程研究与临床康复[J],2007,11(19)：3781-3783.
[14]贺俊平,唐好文,尉秀平.活血化瘀中药对鸡实验性骨折愈合过程血清碱性磷酸酶及骨痂钙盐沉积的影响[J].山西农业大学学报[J],2005,25(2)：119～122.
[15]魏玉玲,王炳南,梁克玉.伤科接骨片对Ⅰ、Ⅱ型胶原基因表达的影响[J].中医正骨,1998,10(5)：3.
[16]董清平,关智宇.骨痛仙胶囊对兔Ⅰ、Ⅱ型胶原蛋白mRNA影响的研究[J].中医药信息,2005,22(1)：50～52.
[17]符诗聪,史炜镔,杜宁,等.丹参有效部位对骨折愈合中胶原基因表达的影响[J].中国中西医结合杂志.2000,20(4)：269.
[18]顾坚毅,汤荣光.新伤续断汤对骨折愈合中胶原影响的实验研究[J].中国中医骨伤科 杂志,200,9(4)：28.
[19]张俐,曾勤,李楠.活血化瘀汤影响成骨细胞功能的实验研究[J].中国中医骨伤科杂志,2004,12(1)：1～4.
[20]王俊勤,胡有谷,郑洪军,等.淫羊藿甙对体外培养成骨细胞增殖和分化的影响[J].中国临床康复,2002,6(9)：1307-1308.
[21]黄长联,董海辉,周建光,等.跌打接骨片促进实验性骨折愈合的骨组织形态剂量学研究[J].中医药研究,2001,17(4)：47～49.
[22]阮朝阳,祁开泽.中药促进骨折愈合作用机制的实验研究进展[J].湖南中医药导报,2003,9(2)：48～49.
[23]刘道德,王凡,李健,等.淫羊藿对家兔骨折愈合影响的研究[J].四川解剖杂志,2004,12(2)：101～105.
[24]徐展望,张建新,谭国庆,等.中药骨碎补提取液对兔骨髓基质细胞体外成骨分化的影响[J].中医正骨,2006,18(6)：15～16.
[25]程杰,余渊,彭锐,等.生骨注射液对大鼠成骨细胞BMP-2mRNA表达影响的实验研究[J].中国中医骨伤科杂志,2005,13(2)：33～36.
[26]梁文,邱辉,黄世章,等.接骨宝促进骨折愈合的实验研究.中医正骨,2004,16(3)：9～12.
[27]袁本祥,吴从俊,熊敦善.骨愈注射液促进骨折愈合的实验研究[J].中国中医骨伤科杂志,2002,10(3)：13～17.
[28]孙之镐,刘向前,祁开泽,等.接骨紫金丹对家兔骨折愈合期间几种金属元素的影响[J].中国骨伤,1999,12(6)：16～18.
[29]赵晓莲,翟饶生,李晶,等.红花对家兔实验性骨折愈合中锌铜含量的影响[J].黑龙江医药科学,2004,27(2)：43～44.
[30]吴从俊,袁本祥,熊敦善.骨愈注射液对家兔骨折愈合影响的实验研究[J].中国中医骨伤科杂志,2002,10(6)：10～13.
[31]刘进.张雪华.氟化钠、自然铜、维生素C成骨效果的实验研究[J].临床口腔医学杂志,1997,13(4)：224.
[32]张克勤,刘湘秀,李瑞宗.七厘散对骨折愈合作用的初步实验研究[J].中华外科杂志,1962,10(5)：305.
[33]柳海峰,杨荪,陈晋杰,等.三花接骨散对骨折鼠垂体生长激素细胞的影响.中国中医骨伤科杂志[J],1998,6(5)：7.
[34]侯晓峰,刘景生.中药促进骨折愈合机理.中国中医骨伤科杂志[J],2003,2(11)：61.
[35]李昕,王集锷.雌激素对去势SD雌性大鼠骨折愈合早期骨痂形成影响的实验研究[J].中国矫形外科杂志,1999,6(7)：524～525.
[36]王毅,于顺禄,郭若霖,等.重组人甲状旁腺激素(1-34)片段促进动物骨折愈合的研究[J].天津医药,2006,34(12)：880～883.
[37]刘献祥,余希杰,许书亮.无名异冲剂在骨折愈合中对DNA和BMP含量影响的实验研究[J].中国骨伤,1999,12(3)：21.
[38]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响[J].辽宁中医杂志,2005,32(4)：374～376.
[39]王志文,张爱国,袁强,等.麝香乌龙丸对家兔骨折BMD、BMC、BMP的作用研究[J].四川中医,2006,24(12)：1112.
[40]沈霖,林燕萍,王拥军编.骨伤科试验研究(M).第一版,北京科学技术出版社,2005.187.
[41]郑智勇.接骨冲剂对骨形成蛋白和骨痂细胞DNA含量变化的影响[J].临床与实验病理学杂志,1998,14(4)：583.
[42]汤耿民,沈霖,涂意辉,等.补肾活血方对成骨细胞生长因子TGF-β1mRNA表达的影响[J].中国中医骨伤科杂志,1999,7(5)：5.
[43]刘涛,冉德洲.活血化瘀、补肾益气中药对大鼠骨折愈合中TGF-β1的影响[J].成都体育学院学报,2002,28(1)：92～96.
[44]沈霖,杜靖远,曾晖,等.补肾方对成骨细胞生长因子TGF-β1mRNA表达的影响[J].中国中医骨伤科杂志,2001,13(5)：259.
[45]姬洪全,党耕町,马庆军,等.骨折愈合过程中转化生长因子p表达的实验研究[J].中华外科杂志,1998,36(2)：73.
[46]张俐,杨宗宇,李楠,等.活血化瘀汤对大鼠骨折愈合中转化生长因子-β1mRNA与蛋白表达及软骨内成骨的作用[J].中国临床康复,2006,10(31)：40-42.
[47]熊辉,左亚杰,罗志勇,等.桃红四物汤对实验性骨折愈合过程中VEGFmRNA表达的影响[J].中医正骨,2004,16(4)：8-9.
[48]高云,董福慧,郑军.海螵蛸对骨愈合相关基因表达的影响[J].中医正骨,2004,16(7)：1～3.
[49]刘涛,冉德洲.活血化瘀、补肾益气中药对大鼠骨折愈合中TGF-β1的影响[J].成都体育学院学报,2002,28(1)：92～96.
[50]刘道德,王凡,李健,等.淫羊藿对家兔骨折愈合影响的研究.四川解剖杂志,2004,12(2)：101～105.
[51]史达,许潇.生骨紫金丹在骨折愈合过程中对TGF-β1bFGF影响的实验研究[J].中医药学刊,2006,24(10)：1875～1877.
[52]刘英杰,翁凤泉,李强,等.活血驳骨丸对骨折后内源性bFGF分泌及早期骨痂质量的影响[J].中国中医骨伤科杂志,2004,12(6)：11～14.
[53]李强,王希平,李鄂,等.活血驳骨丸对内源性bFGF分泌影响的探讨[J].放射免疫学杂志,2006,(1)：39～40.
[54]汤耿民,沈霖,夏志道,等.补肾活血方对实验性骨折愈合过程中IGF-Ⅰ的影响[J].中国中医骨伤科杂志,2000,8(3)：1.
[55]徐荣辉,朱雅萍,柴本甫.丹参注射液对鸡胚额骨分离细胞培养生长影响的组织化学观察成骨细胞样细胞的发育与成熟[J].中华骨科杂志,1994,14：185.
[56]冯秋珍,李曼君,叶根梅,等.丹参注射液对体外培养家兔关节软骨细胞的影响[J].湖北中医学院学报,2003,5(3)：17.
[57]柴本甫,汤雪明,李慧.骨折Ⅱ期愈合过程中的成纤维细胞成骨[J].中华骨科杂志,1996,16：245.
[58]史炜镔,符诗聪,杜宁,等.丹参有效部位对骨折愈合过程中胶原基因表达的影响[J].中国中西医结合杂志,2000,20(4)：269.
[59]秦军志.丹参对大鼠胫骨骨折早期愈合过程中血清、骨痂及骨组织中钙、锌、铜的影响[J].中国中西医结合杂志,1992,12(6)：354.
[60]贺旭峰,沈强.丹参及其相关制剂对促进骨折愈合的国内研究进展[J].中国骨伤,2007,20(6)：426～427.
[61]赵晓莲,翟饶生,李晶,等.红花对家兔实验性骨折愈合中锌铜含量的影响[J].黑龙江医药科学,2004,27(2)：43.
[62]崔永锋,张永斌,李刚,等.杜仲对兔骨折愈合影响的光镜观察实验研究[J].中国比较医学杂志,2005,15(3)：154.
[63]郑军,董福慧,程伟.水蛙对骨愈合相关基因表达影响[J].中国骨伤,2003,16(9)：513.
[64]王华松,黄琼霞,许申明.骨碎补对骨折愈合中血生化指TGF-β1表达的影响[J].中医正骨,2001,13(5)：6.
[65]鲍善芬,赵霖,刘玉杰,等.金属铜对骨折愈合作用的实验研究[J].中华外科杂志,2002,40(7)：538.
[66]程志安,吴燕峰,黄智清,等.续断对成骨细胞增殖、分化、凋亡和细胞周期的影响[J].中医正骨,2004,16(12)：1.
[67]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响.辽宁中医杂志[J],2005,32(4)：374.
[70]高云,董福慧,郑军.海螵蛸对骨愈合相关基因表达的影响[J].中医正骨,2004,16(7)：1.
[71]张国文,李晓玲.中药中7种微量元素的测定[J].微量元素与健康研究,1998,15(2)：44.
[72]覃旭.马钱子促进骨折愈合的研究进展[J].贵阳中医学院学报,2006,29(2)：67.
[72]陆炳全,黄素碧,贺景国等.自然铜促进骨折愈合实验研究[J].中外健康文摘,2006,3(9)：77.
[73]周琦百,黄枫,郑晓辉.补肾接骨口服液促进骨折愈合60例疗效观察[J].中国中医骨伤科杂志,2005,6(3)：31～33.
[74]张治国,崔大领.“张氏接骨散’,促进骨折愈合的临床观察[J].中医药研究,1995,15(5)：9.
[75]朱以锦.化痰祛瘀补肾治疗股骨颈骨折延迟愈合30例[J].四川中医,2002,20(12)：63.
[75]蒋顺琬,杨卓欣,林志文.壮筋补骨丸促进骨折愈合的临床研究[J].广州中医药大学学报,2004,2(15)：373.
[76]田玉环,付爱平,刘国胜.正奇接骨丹颗粒剂治疗创伤骨折临床研究[J].中国实验方剂学杂志,2004,10(4)：61.
[77]高锦麟,许祥生.消肿接骨糖浆治疗骨折319例临床观察[J].陕西中医学院学报,1994,17(2)：181.
[78]白礼河,白理智,董引娣,等.生骨散促进骨折愈合作用的临床观察[J].中医正骨,1995,7(3)：101.
[79]刘滨生.中药生肌散治疗开放性骨折合并软组织缺损的疗效观察[J].中医药学报,2002,30(4)：37.
[80]汤耿民,王胜利,王和鸣,等.三花接骨散促进骨折愈合临床实验研究[J].中国中医骨伤科杂志[J],1995,3(3)：161[81]陈晋杰,潘少川,张连柱,等.三花接骨散治疗骨折的实验性报告[J].北京医学,1995,17(1)：581.
[82]匡建华.接骨理伤汤促进骨折愈合50例[J].湖南中医杂志,2003,5,19(3)：19.
[83]吴官保.跌打促愈片治疗胫腓骨骨折46例[J].湖南中医杂志,2002,7,18(4)：13.
[84]贾恩礼.中药“生骨胶囊”治疗骨折及股骨头坏死的临床效果[J].实用医药杂志,2002,10,19(10)：778～779.
[85]张越林,牛惠敏.中药治疗骨折延迟愈合的临床观察[J].天津中医,1996,13(2)：241.
[86]任桂兰.阳和汤合剂治疗骨折延迟连接疗效观察[J].中医正骨,1999,11(2)：111.
[87]谭德雄.金锁固精丸治疗骨折迟缓愈合22例报告[J].中国中医骨伤科杂志,1991,7(2)：441.
[88]郑祖纯.白蛤健骨丸治疗骨折迟缓愈合147例[J].内蒙古中医药,1993,(4)：51.
[89]杨海韵,陈逊文,陈志维,等.“骨宝丸”促进骨折愈合作用的临床疗效观察和实验研究[J].中国中西医结合外科杂志,1996,3：203-205.
[90]周成刚.正骨丹促进骨折愈合疗效观察[J].中国中医骨伤科杂志,2003,11(1)：19.21.
[91]陈玲,杨云洲,陈继革,等.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[92]沈祥春,张贵林,任光友,等.抗骨折方促进实验性大鼠骨折愈合作用的研究[J].中华中医药杂志,2007,22(5)：285-288.
[93]王银环,韩淑英,朱丽莎,等.双黄冲剂对兔骨折愈合的实验研究[J].华北煤炭医学院学报,2008,10(5)：585～586.
[94]卞俊,陈海飞,宣伟东等.愈骨疗伤胶囊促进骨折愈合的药效学实验[J].中成药[J],2008,30(11)：1682.
[95]陈世同.挫伤接骨膏治疗创伤骨折555例临床总结[J].江苏中医,1990,11(9)：221.
[96]杨力.接骨膏对骨折愈合作用的探讨[J].河北中医,1995：17(4)：271.
[97]孙炳烈,赵然,王梦娟等.明氏外用接骨膏促进骨折愈合的实验研究[J].中国中医骨伤科杂志,1990,6(4)：4.
[98]焦志国.生骨丹外敷内服治疗骨折延迟愈合和骨不连的疗效分析[J].中国现代药物 应用,2009,3(10)：131.
[99]侯莜魁,石关桐,赵敏辉等.外敷中药对家兔桡骨骨折愈合的影响[J].中国中医骨伤科杂志,1992,13(2)：10.
[100]谢明夫,苏庆洋,刘丽清.外用“接骨散”治疗四肢骨折迟缓愈合25例[J].菏泽医学专报,1999,11(1)：62.
[101]袁昌锦,付天明,刘敏等.中草药接骨膏对家兔创伤性骨折愈合作用的实验研究[J].四川中医,2005,23(10)：34-36.
[102]江树连,丁锷,李保泉.消瘀接骨散外敷对家兔骨折愈合影响的实验研究[J].中医外治杂志,2000,9(3)：34～36.
[103]张建国.活血消肿接骨散对兔骨折愈合骨痂强度的影响[J].中医正骨,2002,14(9)：522～523.
[104]翟献斌,王宗辉.泰山接骨膏治疗骨折的临床研究[J].中医正骨,2007,19(4)：11～12.
[105]陶志东,孙成长,毛伟欢.消肿散瘀膏外敷治疗骨折158例[J].山东中医杂志,2009,28(9)：11～12.
[106]熊芳丽,肖亚平,针灸促进骨折愈合的临床观察.中国针灸,1997,17(11)：6851.
[107]邹志军,张建军,马凤英,等.巨刺疗法对股骨颈骨折延迟愈合的疗效观察.中国中医骨伤科杂志,1991,7(3)：321.
[108]张作君,赵然,成传德,等.针刺、艾灸促进骨折愈合的实验研究[J].中医正骨,1992,4(2)：71.
[109]刘滨生.前臂骨折后期的辅助针刺疗法[J].针灸临床杂志,2002,18(6)：16.
[110]李心沁,王琳,单秋华.针刺对大鼠骨折愈合及骨痂TGF-β1表达的影响[J].山东中医杂志,2006,25(8)：546～548.
[111]刘家瑞.穴位注射配合物理疗法治疗胸腰椎压缩性骨折[J].中国康复,2006,21(3)：198.
[112]周黎明.电针治疗胫骨骨折迟缓愈合52例疗效观察[J].中国针灸,2000(10)：599-600.
[113]王全权,陈海林,张兴国.穴位注射结合中药促进尺桡骨骨折愈合的疗效观察[J].成都中医药大学学报,2005,28(2)：23-24.
[114]卢敏,谢进,戴致波.小针刀对兔骨折愈合影响的实验研究[J].湖南中医药大学学报,2007,27(4)：70～72.
[115]卢敏,戴致波,谢进.小针刀治疗对骨折愈合血管内皮细胞生长因子表达及血清无机盐和碱性磷酸酶影响的实验研究[J].中国中医骨伤科杂志,2007,15(6)：9-11.
[116]孙维琰,黎君若,王素芳,等.中药电热夹板促进骨折愈合的临床研究[J].中国中医骨伤科杂志,1991,7(4)：121.
[117]孙炳烈,郭建刚,赵然,等.中药电热夹板促进骨折愈合的实验研究.中国中医骨伤科杂志,1991,7(4)：151.
[1]邹声泉,龚建平.外科学-前沿与争论[M].北京：人民卫生出版社.2003,815-836.
[2]Issack PS, Di sesare PE. Recent advances toward the Clinical application of bone morphogenetic proteins in bone and repair. Am J Orthop. Am J Orthop[J].2003,32 (9): 429-436.
[3]Szczesny G. Growth factors in bone. Int Orthop[J].1998,22 (6):410-416.
[4]Chen D, Harris MA. BMP-2 enhances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation in cultures of fetal rat calvarial osteoblasts[J].. Calcif TissueInt,1997,60(3):283.
[5]Onishi T, Ishidou Y, Nagamine T, et al. Distinct and over lapping patterns of localization of bone morphogenetic protein family members and a BMP type Ⅱ receptor during fracture healing in rat s. Bone,1998,22:605.
[6]曾中华,余黎,龚玲玲,等.骨折愈合过程中BMP-2和VEGF的表达[J].武汉大学学报.2005,26(4)：467～469.
[7]朱六龙,戴克戎.骨形成蛋白22基因转染人骨髓间质干细胞诱导异位成骨的实验研究[J].中国修复重建外科杂志.2003,17(2)：131—135.
[8]尹战海,王坤正,张沈荣,等.骨形成蛋白增强自体骨修复股骨头骨缺损的研究[J].中国修复重建外科杂志,2002,16(2)：93-96.
[9]ZabkaAG, PluharGE, Edwards RB 3rd, et al. Histomorphometric descriptin of allograft bone remodeling and union in a canine segmental femoral defect model:a comparison of rhBMP-2, cancellous bone, and absorbable collagen sponge[J]. J Orthop Res,2001, 19(2):318—327.
[10]Rnhe PQ, Kroese-Deutman HC, wolke JG, et al. Bone inductive properties of rhBMP-2 loaded po rous calcium phosphate cement implants incranial defects in rabbits[J]. Biomaterials,2004,25(11):2123—2132.
[11]杜俊杰,等.p转化生长因子增强人重组骨形发生蛋白-2诱导成骨的调节机理[J].中国矫形外科杂志,1998,(5),6：536.
[12]Maliakal JC, Asahina I, Hauschika PV et al. Osteogenic protein-7(BMP-7)inhibits cell proliferation stimulates the expression of makers characteristic of osteoblast phenotype in rat osteosarcoma cells[J]. Growth Factors,1994;11 (3):227.
[13]张永刚,卢世璧,王继芳.骨引导与骨诱导[J].中华创伤杂志,1996,31(1)：1992209.
[14]Okubo Y. BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest[J]. Development,2000,2962(5):109521104.
[15]Sakou T. Bone morphogenetic proteins:from basic studies to clinical approaches[J]. Bone,1998,22 (6):5912603.
[16]Dragoo. Newest factors in fracture healing[J]. Clin Orthop,1992,27 (7):297-311.
[17]A st rom A K, J in D, Imamura T, et al. Current concepts growth factors in bone[J]. IntOrthopedics,1998 (22):410-416.
[18]Chen D, Harris MA. BMP-2 enchances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation in cultures of fetal tat calvarial osteo blasts[J]. Calcif Tissue Int (inpress),2003, (12):2102216.
[19]刘健,胡蕴玉,马真胜,等.骨折愈合过程中BMP-3基因表达的实验研究[J]中华外科杂志,1996,34(10)：585-587.
[20]Ghosh-Choudhury N, Harris MA,Chen D,et al. Transfection of BMP-2 expression plasmial induces osteoblastic differentiation in a BMP-2 dependent preosteoblast cell line[J].J Bone Miner Res,2004,9(suppl1):137.
[21]Stone CA. Amo lecular approach to bone regeneration[J]. British J Plastic Surgery,2003, 50(5):369-373.
[22]Reddi A H. Morphogenes is and tissue engineering of bone andcartilage:inductive signals, stem cells,and biomimetic bioma-terials[J]. Tissue Eng,2000,6 (4):351-359.
[23]张子军,卢世璧,王继芳,等.骨缺损中内源性BMP的分布及其作用[J].中华外科杂志,1996,34(10)：596-597.
[24]Kubler N, Urist MR. Clin orthop.1998,292:321-328.
[25]Miyamoto S, Takaoka K etal. Calcif Tissue Int,1992,50(suppl1):15.
[26]Reddi AH. Bone morphogenetic proteins, bone marrow stromal cells, and mesenchymal stem cells. Clin Orthop,200,313):115-119.
[27]Einhorn TA, Majeska RJ, Mohaideen A, et al. A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair[J]. J Bone Joint Surg Am,200385-A (8):1425-1435.
[28]Sheehan JP, Sheehan JM, Sheehan JM H, et al.The safety and utility of recombinant human bone morphogenetic protein-2 for cranial procedures in a nonhuman primate model.[J].J Neursurg,2003,98 (1):125-130.
[29]苏佳灿,许硕贵,张春才.生长因子与骨重建研究进展[J].临床骨科杂志,2001,4(2)：155.
[30]Yee JA, Yan L, Domin JC etal. Plasminogen dependent activation of latent transforming growth factor beta by growing cultures of osteoblast-like cells[J]. J Cell Physiol,1993, 157(5):528-534.
[31]Oreffo RO, Bonewald L, Kukita A et al. Inhibitory effects of the bone-derived growth factors osteoinductive factor and transforming growth factor-beta on iso-lated osteoclasts [J].Endocrinology,1990,126 (10):69～75.
[32]Bolander ME. Regulation of fracture repair by growth factors[J]. Proc Soc ExpBiol Med, 1992,200(2):165～170.
[33]Joyce ME, Terek RM, Jingushi S et al. Role of transforming growth factor-betain fracture healing [J].Ann N Y AcadSci,1990,593 (1):107～123.
[34]Sandberg MM, Aro HT, Vuorio EL etal. Gene expression during fracture repair[J]. Clin Orthop,1993, (289):292～312.
[35]Shuto T, Sarkar G, Bronk J T et al. Osteoblasts express type Ⅰ and Ⅱ activin receptors during early intramembranous and endochondral bone formation [J] JBone Miner Res, 1997,12(3):403～411.
[36]Whitman M. Feedback from inhibitory SMADs[J].Nature,1997,389 (4):549～551.
[37]Beck LS, Deguzman L, Wyne LP et al. TGF-beta-2 induces bone closure of skull defects [J]. J Bone Miner Res,1991,6 (8):1257～1265.
[38]Critchlow MA, Bland YS, Ashahurst DE et al. The effects of age on the response of rabbit periosteal osteoprogenitor cells to exogenous transforming growth factor beta-2[J]. J Cell Sci,1994,107(4):499～516.
[39]Nielsen HM, Andreassen TT, Ledet T et al. Local injection of TGF-beta increases the strength of tibial fractures in the rat [J]. Acta Orthop Scand,1994,65 (1):37～41.
[40]Lind M, Overgaard S, Nguyen T et al. Transforming growth factor2beta stimulates bone ongrowth:hydroxyapatitecoated implants study in dogs [J]. Acta Orthop Scand,1996, 67(5):611～616.
[41]Joyce ME, RobertsAB, SporeMB, et al. Transforming growthfactor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur[J]. J Cell Biol,1990,110(6): 2195-2207.
[42]田卫东,王大章.生长因子网络调节对骨形成作用的研究[J].华西口腔医学杂志,1998,16(2)：65～72.
[43]Farhadieh RD, Dickinson R, Yu Y, et al. The role of transforming growth factor-beta, insulin-like growth factor I, and basic fibroblast growth factor in distraction osteogenesis of the mandible[J]. J Craniofac Surg,1999,10:80.
[44]田卫东,王大章,乔鞠,等.生长因子网络调节对骨形成作用的研究：bFGF对人胚成骨样细胞增殖及分化的影响[J].华西口腔医学杂志,1998,16(4)：344～347.
[45]龚振字,周树夏,曹建广,等.碱性成纤维细胞生长因子对兔下颌骨骨折愈合中细胞增殖的影响[J].实用口腔医学杂志,2007,11(5)：385～387.
[46]Amizuka N, Davidson D, Liu H, et al. Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilageand bone development[J]. Bone,2004,34(1):13～25.
[47]Walsh S, Jeferiss C, Stewart K, et al. Expression of the developmental makers STRO-1 and alkaline phosphatase in cultures of hunman marrow stromal cells:regulation by fibroblast growth factor(FGF)-2 and relationship to the expression of FGF receptors 1-4[J]. Bone,2000,27(2):185～195.
[48]Globus RK, Pat terson2Buckendahl P, Gospodarowicz D1 Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta[J]. Endocrinology,1988,123:98～1051.
[49]Canalis E, Cent rella M, McCart hy T. Effect of basic fibroblast factor on bone formation in vitro [J]. J Clin Invest,1988,81:1572～1577.
[50]Iwasaki M, Nakahara H, Nakata K, et al. Regulation of proliferation and osteochondrogenic differentiation of periosteumderived cells by transforming growth factor beta and basic fibroblast growth factor [J]. J Bone Joint Surg (Am),1995, 77:543-554.
[51]Kawaguchi H, Kurokawa T, Hanada K, et al. Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin2diabetic rats. Endocrinology,1994,135:774-781.
[52]王立平,党耕町.碱性成纤维细胞生长因子在骨愈合过程中的表达与合成[J].中华骨科杂志,1999,19(8)：488～490.
[53]Baddoo M, Hill K, Wilkinson R, et al. Characterization of mesenchymal stem cells isolation from murine bone marrow by negative selection[J]. J Cell Biochem,2003, 89:1235～1249.
[54]Lisignoli G, Fini M, Giavaresi G, et al. Osteogenesis of large segmental radius defects enhanced by basic fibroblast growth factor actirated bone marrow stromal cells grown on non-woven hyaluronic acid-based polymer scaffold[J]. Biomaterials,2002, 23:1043～1051.
[55]Schmal H, Mehlhorn A T, Fehrenbach M, et al. Regulative mechanisms of chondrocyte adhesion [J]. Tissue Eng,2006,12:741～750.
[56]Wong W C, Yu X, Wallace A L, et al. Use of a polymeric device to deliver growth factors to a healing fracture [J]. ANZ J Surg,2003,73:1022～1027.
[57]Pacicca DM, Patel N, Lee C, et al. Expression of angiogenic factors during distraction osteogenesis[J]. Bone,2003,33:889～898.
[58]Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in t he regula2tion of osteoblast function and bone growt h[J] Development,2003,130:306323074.
[59]Clarke S A, Brooks R A, Lee P T, et al. The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant [J]. J Ort hop Res,2004, 22:1016～1024.
[60]Kawaguchi H, Nakamura K, Tabata Y, et al. Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2[J]. J Clin Endocrinol Metab,2001, 86:875～880.
[61]Kawaguchi H, Nakamura K, Tabata Y, et al. Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2 [J]. J Clin Endocrinol Metab,2001, 86:875～880.
[62]Montero A, Okada Y, Tomita M, et al. Disruption of the fibroblast growth factor-2 gene result s in decreased bone mass and bone formation[J]. J Clin Invest,2000, 105:1085～1093.
[63]Debiais F, Lefevre G, Lemonnier J. Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-ki-nase-dependent,beta-catenin-independent signaling pathway[J].Exp Cell Res,2004,297:235-246.
[64]Fukuda A, Kato K, Hasegawa M, et al. Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast factor [J]. Biomaterial s, 2005,26:4301-4308.
[65]Linkhant TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair:IGF, TGFβand BMP[J]. Bone,1996,19:1. [66] Kanzaki S, Hilliker S, Baylink DJ, et al. Evidence that HBC in culture produce IGFBP-4 and-5 proteases [J]. Endocronology, 1994,134:383.
[67]Brown DJ, kaoWW, Greenhalgh DG. apoptosis down-regulates inflame mation under the advancing ep ithelial wound edge:delayed patterns indiabetes and improvement with topical growth factors [J]. Surgery,1997,12 (14):372.
[68]Shenaq SM, Rabinovsky ED. Gene therapy for plastic and reconstructive surgery J [J]. Clin Plast Surg,1996,23 (1):157.
[69]JeschkeM G, Barrow R E, Hawkins H K. Effect of multiple gene transfers of in sulin like growth factor I complementary DNA gene constructs in rats after thermal injury[J]. Arch Surg,1999,134(10):1137.
[70]Eming SA, Lee J, Snow Rg, et al. Genetically modified human epidermis over-expressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice:implications for the use of genetically modified keratinocytes tomodulate dermal regeneration[J]. J Invest Dermatol,1995,105:756.
[71]吉建新,廖伟娇,邱志辉,等.碱性成纤维细胞生长因子和胰岛素样生长因子-1对牙周膜细胞增殖的影响[J].广州医药杂志,2005,26(5)：606
[72]Andrew JG, Hoyland J, Freemont AJ, et al. Insulin-like growth factor gene expression in human fracture callus[J]. Calcif Tissue Int,1993,53(2):97.
[73]McCarthy TL, J i C, Casinghino S, et al. Alternate signaling pathways selectively regulate binding of insulin-like growth factor Ⅰ and Ⅱ on fetal rat bone cells[J] J. Cell Biochem,1998,68 (4):446.
[74]Murphy Mg, Bach MA, Plotkin D, et al. Oral administra-tion of the growth hormone secretagogue MK-677 in-creases markers of bone turnover inhealthy and functional-ly impaired elderly adults. TheMK-677 Study Group [J]. J BoneMiner Res,1999,14 (7):1182.
[75]李亚非,李青,马福成.人骨折骨痂中胰岛素样生长因子Ⅰ的免疫组化研究[J].中华实验外科杂志,1997,14(3)：191.
[76]王振海,付勤,赵忠海.EGF和IGF对体外培养兔关节软骨细胞的影响[J].中国骨伤,2003,16(1)：23.
[77]刘刚,胡蕴玉,马平,等.胰岛素样生长因子-Ⅰ对兔关节软骨细胞增殖及代谢的影响[J].中国修复重建外科杂志,2002,16(4)：228.
[78]Kudo-Y, Iwashita-M, iguchi-T, et al. The regulation of type-1 collagen synthesis by insulin-like growth factor-1 in human osteoblast-like SaOS-2 cells[J]. P flugers-Aarch, 1996,433 (1-2):123.
[79]Ferrara N, Henzel WJ. P ituitary Fo llicular cell secrete a novel heparin-binding growth factor specific for vascular endo thelial cells [J]. Biochem Biophys Res Commun,1989; 161 (2):8512858.
[80]Conno lly DT, Heuvel man DM, N elson R. et al. Tumor Vascular permeablility factor stimulates endothelial cell growth and angio lgenesis [J]. J Clin Invest,1989; 84: 1470～1478.
[81]Street JT, W ang JH, W u QD, et al. The angiogenic response to skeletal injury is p reserved in the elderly[J]. J O rthop R es,2001,19 (6):1057～1066.
[82]Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor. an endothelial cell mitogen related to PDGF [J]. S cience,1989,246:1309～1312.
[83]Homer A, B ishop NJ, Bo rd S, et al. Immune localisation of vascular endo thelial growth factor (VEGF) in human neonatal growth plate cartilage[J]. J A nat,1999; 194 (4): 519-524.
[84]Pufe T, Peterson W, T illmann B, et al. The angiogenic peptide vascular endo thelial growth factor is expressed in foetal and ruptured tendons [J]. J V irchow s A rch,2001; 439 (4):579～585.
[85]Gerstenfeld LC, Cullinance DM, Barnes GL, et al. Fracture healing as a post-natal developmental process:molecular spatial and temporal aspects of its regulation [J]. J Cell Biochem,2003; 88 (5):873～884.
[86]Hayam i T, Funaki H, Yaoeda K. Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis [J]. J R heum atol,2003; 30(10):2207～2217.
[87]钟刚,裴福兴,樊瑜波,等.V EGF基因转染促进骨折愈合的实验研究[J].中国矫形外科杂志,2004；12(8)：604～609.
[88]杨操,杨述华,杜靖远,等.V EGF基因转染促进股骨头坏死修复[J].临床骨科杂志,2004；7(1)：90～93.
[89]初同伟,王正国,朱佩芳,等.骨折愈合过程中血流量的变化与VEGF的相关性研究[J].中国矫形外科杂志,2002；9(6)：577～579.
[90]Street J, Bao M, Guzman L, et al. Vascularendo thelial growth stimulates bone repair buromo ting angiogenesis and bone turnover [J]. Proc Natl Acad Sci USA,2002; 99 (15):9656～9661.
[91]Peng H, W right V, U sas A, et al. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4[J]. J C lin Inv est,2000; 110 (6):751～759.
[92]M usch ler GF, N akamo to C, Griffith L G, et al. Engineering principles of clinical cell-based tissue engineering [J]. J B one Joint Surg A m,2004,86-A (7):1541～1558.
[93]Lattermann C, Baltzer AW, Zelle BA, et al. Feasibility of percutaneous gene transfer to anatrophic nonunion in a rabbit [J]. J orthop Res,2004,425 (8):237-243.
[94]刘日光,尹培荣,杨述华,等.人VEGF 165基因在狗脊髓细胞中的表达[J].中国矫形外科杂志,2004,12(19)：1476～1478.
[95]杨述华,杨操,许伟华,等.人血管内皮生长因子的cDNA克隆及其在兔成骨细胞中的表达[J].中华骨科杂志,2002；20(2)：99～102.
[96]王代友,于大海,邝晓聪,等.人血管内皮生长因子基因的克隆及其真核表达质粒的构建[J].广西医科大学学报,2004,21(1)：8-10.
[97]初同伟,王正国,朱佩芳,等.骨折愈合过程中VEGF及其受体的表达[J].中华创伤杂志,2001,17(6)：344～346.
[98]刘杰,孙正义,曹蕾,等.血管内皮生长因子对生物衍生骨复合骨髓基质细胞体内成骨的影响[J].中国临床康复,2003,7(11)：1622～1623.
[99]钟刚,裴福兴,樊瑜波,等.VEGF基因转染促进骨折愈合的实验研究[J].中国矫形外科杂志,2004,12(8)：604～609.
[100]鱼兵,闫露,范清宇,等.人BMP-7及VEGF 165基因共表达腺病毒的构建及在兔骨髓基质干细胞中的共表达[J].中国矫形外科杂志,2004,12(21-22)：1704～1707.
[1]柴本甫,过邦辅.理气药物对骨折愈合的影响的初步研究.中华外科杂志,1962,10(5)：299.
[2]李光辉,陈超.伤科接骨片对家兔骨折后血液流变性的影响[J].中国中医急症,2003,12(1)：61.
[3]陈玲,杨云洲,陈继革.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[4]张金海,张伟成.补肾活血合剂促进骨折愈合的实验研究[J].现代中西医结合杂志,2007,16(10)：1321～1322.
[5]刘进.张雪华.氟化钠、自然铜、维生素C成骨效果的实验研究[J].临床口腔医学杂志,1997,13(4)：224.
[6]张克勤,刘湘秀,李瑞宗.七厘散对骨折愈合作用的初步实验研究[J].中华外科杂志,1962,10(5)：305.
[7]毛弋平.谈自然铜炮制方法[J].现代应用药学,1994.11(3)：17.
[8]王静,毛春芹,陆兔林,等.中药醋制法研究进展[J]中国中医药信息杂志,2009,16(1)99-101.
[9]张冒颖.生物化学[M].北京：人民卫生出版社,1987.589.
[10]薛少汀,葛宝丰,徐印坎,等.实用骨科学[M],北京：人民军医出版社.2005,29.
[11]北京医学院主编.生物化学[M].北京：人民卫生出版社,1978.497-498.
[12]董华,胡乃武,董清平,等.骨痛仙胶囊对家兔骨折血清碱性磷酸酶、钙、磷影响的实验研究[J].中医药学报,2003,2(31)：51-52.
[13]袁强,志文,张爱国,等.麝香乌龙丸对兔实验骨折Ca、P、ALP的作用研究[J].陕西中医,2006,27(11)：1443-1442.
[14]周晶亚.中草药接骨膏促进骨折愈合作用的实验研究[J].时珍国医国药,2008,19(8)：2014～2015.
[15]林军,王慧明,曹之强,等.下颌骨缺损修复过程中Ⅰ型胶原基因表达的实验研究[J].中国口腔种植医学杂志,2001,6(1)：7-10.
[16]曾岩,马庆军,郭昭庆,等.骨髓基质细胞体外培养成骨能力的实验研究[J].中华骨科杂志,2001,21(1)：45～49.
[17]Robert s AB, Sporn MB, Assion RK, et al. Transforming growth factor2β:rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA[J],1986,81(4):167.
[18]Chen D, Harris MA.BMP-2 enhances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation incultures of fetal rat calvarial osteoblasts. Calcif Tissue Int[J],1997,60 (3):283.
[19]Onishi T, Ishidou Y, Nagamine T, et al. Distinct and over lapping patternsof localization of bone morphogenetic protein family members and a BMP type Ⅱ receptor during fracture healing in rats. Bone[J],1998,22:605.
[20]韩立军,王俊红,孙建国,等.中药治疗骨折的两阶段学说及临床研究.河北中医药学报,2000,15(1)：12～14.
[2]叶维建,郑玉涛.活血散促进骨折愈合的试验研究[J].牡丹江医学院学报,2005,26(5)：23～25.
[3]李光辉,陈超.伤科接骨片对家兔骨折后血液流变性的影响[J].中国中医急症,2003,12(1)：61.
[4]赵志强,王体沛,王俊芳.丹参与川芎嗪对家兔骨折后血液流变学的影响[J].华中医学杂志,2005,29(5)：374～375.
[5]张志敬,周辉,赵万军,等.和胃接骨胶囊促进试验性骨折的超微结构观察[J].中国中医骨伤科杂志2007,15(3)：26～29.
[6]陈玲,杨云洲,陈继革.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[7]张金海,张伟成.补肾活血合剂促进骨折愈合的实验研究[J].现代中西医结合杂志,2007,16(10)：1321～1322.
[8]罗佩强.土鳖虫促进骨折愈合的实验研究[J].中国骨伤,1992,5(6)：61.
[9]阮朝阳,祁开泽.中药促进骨折愈合作用机制的实验研究进展[J].湖南中医药导报,2003,9(2)：48～49.
[10]高越,胡海翔.复合中药制剂促进大鼠骨折愈合的实验研究[J].科学技术与工程,：2007,7(6)：1164～1166.
[11]董华,胡乃武,董清平.骨痛仙胶囊对家兔骨折血清碱性磷酸酶、钙、磷影响的实验研究[J].中医药学报,2003,31(2)：51～52.
[12]冯坤,陈宝龙,王健智,等.益生接骨颗粒对肾虚骨折家兔骨痂骨矿成分的影响[J].中国中医骨伤科杂志,2005,13(1)：1-4.
[13]谢艳,朱太咏,毕军花,等.益气生骨颗粒对大鼠骨折愈合骨痂中无机质及钙含量的影响[J].中国组织工程研究与临床康复[J],2007,11(19)：3781-3783.
[14]贺俊平,唐好文,尉秀平.活血化瘀中药对鸡实验性骨折愈合过程血清碱性磷酸酶及骨痂钙盐沉积的影响[J].山西农业大学学报[J],2005,25(2)：119～122.
[15]魏玉玲,王炳南,梁克玉.伤科接骨片对Ⅰ、Ⅱ型胶原基因表达的影响[J].中医正骨,1998,10(5)：3.
[16]董清平,关智宇.骨痛仙胶囊对兔Ⅰ、Ⅱ型胶原蛋白mRNA影响的研究[J].中医药信息,2005,22(1)：50～52.
[17]符诗聪,史炜镔,杜宁,等.丹参有效部位对骨折愈合中胶原基因表达的影响[J].中国中西医结合杂志.2000,20(4)：269.
[18]顾坚毅,汤荣光.新伤续断汤对骨折愈合中胶原影响的实验研究[J].中国中医骨伤科 杂志,200,9(4)：28.
[19]张俐,曾勤,李楠.活血化瘀汤影响成骨细胞功能的实验研究[J].中国中医骨伤科杂志,2004,12(1)：1～4.
[20]王俊勤,胡有谷,郑洪军,等.淫羊藿甙对体外培养成骨细胞增殖和分化的影响[J].中国临床康复,2002,6(9)：1307-1308.
[21]黄长联,董海辉,周建光,等.跌打接骨片促进实验性骨折愈合的骨组织形态剂量学研究[J].中医药研究,2001,17(4)：47～49.
[22]阮朝阳,祁开泽.中药促进骨折愈合作用机制的实验研究进展[J].湖南中医药导报,2003,9(2)：48～49.
[23]刘道德,王凡,李健,等.淫羊藿对家兔骨折愈合影响的研究[J].四川解剖杂志,2004,12(2)：101～105.
[24]徐展望,张建新,谭国庆,等.中药骨碎补提取液对兔骨髓基质细胞体外成骨分化的影响[J].中医正骨,2006,18(6)：15～16.
[25]程杰,余渊,彭锐,等.生骨注射液对大鼠成骨细胞BMP-2mRNA表达影响的实验研究[J].中国中医骨伤科杂志,2005,13(2)：33～36.
[26]梁文,邱辉,黄世章,等.接骨宝促进骨折愈合的实验研究.中医正骨,2004,16(3)：9～12.
[27]袁本祥,吴从俊,熊敦善.骨愈注射液促进骨折愈合的实验研究[J].中国中医骨伤科杂志,2002,10(3)：13～17.
[28]孙之镐,刘向前,祁开泽,等.接骨紫金丹对家兔骨折愈合期间几种金属元素的影响[J].中国骨伤,1999,12(6)：16～18.
[29]赵晓莲,翟饶生,李晶,等.红花对家兔实验性骨折愈合中锌铜含量的影响[J].黑龙江医药科学,2004,27(2)：43～44.
[30]吴从俊,袁本祥,熊敦善.骨愈注射液对家兔骨折愈合影响的实验研究[J].中国中医骨伤科杂志,2002,10(6)：10～13.
[31]刘进.张雪华.氟化钠、自然铜、维生素C成骨效果的实验研究[J].临床口腔医学杂志,1997,13(4)：224.
[32]张克勤,刘湘秀,李瑞宗.七厘散对骨折愈合作用的初步实验研究[J].中华外科杂志,1962,10(5)：305.
[33]柳海峰,杨荪,陈晋杰,等.三花接骨散对骨折鼠垂体生长激素细胞的影响.中国中医骨伤科杂志[J],1998,6(5)：7.
[34]侯晓峰,刘景生.中药促进骨折愈合机理.中国中医骨伤科杂志[J],2003,2(11)：61.
[35]李昕,王集锷.雌激素对去势SD雌性大鼠骨折愈合早期骨痂形成影响的实验研究[J].中国矫形外科杂志,1999,6(7)：524～525.
[36]王毅,于顺禄,郭若霖,等.重组人甲状旁腺激素(1-34)片段促进动物骨折愈合的研究[J].天津医药,2006,34(12)：880～883.
[37]刘献祥,余希杰,许书亮.无名异冲剂在骨折愈合中对DNA和BMP含量影响的实验研究[J].中国骨伤,1999,12(3)：21.
[38]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响[J].辽宁中医杂志,2005,32(4)：374～376.
[39]王志文,张爱国,袁强,等.麝香乌龙丸对家兔骨折BMD、BMC、BMP的作用研究[J].四川中医,2006,24(12)：1112.
[40]沈霖,林燕萍,王拥军编.骨伤科试验研究(M).第一版,北京科学技术出版社,2005.187.
[41]郑智勇.接骨冲剂对骨形成蛋白和骨痂细胞DNA含量变化的影响[J].临床与实验病理学杂志,1998,14(4)：583.
[42]汤耿民,沈霖,涂意辉,等.补肾活血方对成骨细胞生长因子TGF-β1mRNA表达的影响[J].中国中医骨伤科杂志,1999,7(5)：5.
[43]刘涛,冉德洲.活血化瘀、补肾益气中药对大鼠骨折愈合中TGF-β1的影响[J].成都体育学院学报,2002,28(1)：92～96.
[44]沈霖,杜靖远,曾晖,等.补肾方对成骨细胞生长因子TGF-β1mRNA表达的影响[J].中国中医骨伤科杂志,2001,13(5)：259.
[45]姬洪全,党耕町,马庆军,等.骨折愈合过程中转化生长因子p表达的实验研究[J].中华外科杂志,1998,36(2)：73.
[46]张俐,杨宗宇,李楠,等.活血化瘀汤对大鼠骨折愈合中转化生长因子-β1mRNA与蛋白表达及软骨内成骨的作用[J].中国临床康复,2006,10(31)：40-42.
[47]熊辉,左亚杰,罗志勇,等.桃红四物汤对实验性骨折愈合过程中VEGFmRNA表达的影响[J].中医正骨,2004,16(4)：8-9.
[48]高云,董福慧,郑军.海螵蛸对骨愈合相关基因表达的影响[J].中医正骨,2004,16(7)：1～3.
[49]刘涛,冉德洲.活血化瘀、补肾益气中药对大鼠骨折愈合中TGF-β1的影响[J].成都体育学院学报,2002,28(1)：92～96.
[50]刘道德,王凡,李健,等.淫羊藿对家兔骨折愈合影响的研究.四川解剖杂志,2004,12(2)：101～105.
[51]史达,许潇.生骨紫金丹在骨折愈合过程中对TGF-β1bFGF影响的实验研究[J].中医药学刊,2006,24(10)：1875～1877.
[52]刘英杰,翁凤泉,李强,等.活血驳骨丸对骨折后内源性bFGF分泌及早期骨痂质量的影响[J].中国中医骨伤科杂志,2004,12(6)：11～14.
[53]李强,王希平,李鄂,等.活血驳骨丸对内源性bFGF分泌影响的探讨[J].放射免疫学杂志,2006,(1)：39～40.
[54]汤耿民,沈霖,夏志道,等.补肾活血方对实验性骨折愈合过程中IGF-Ⅰ的影响[J].中国中医骨伤科杂志,2000,8(3)：1.
[55]徐荣辉,朱雅萍,柴本甫.丹参注射液对鸡胚额骨分离细胞培养生长影响的组织化学观察成骨细胞样细胞的发育与成熟[J].中华骨科杂志,1994,14：185.
[56]冯秋珍,李曼君,叶根梅,等.丹参注射液对体外培养家兔关节软骨细胞的影响[J].湖北中医学院学报,2003,5(3)：17.
[57]柴本甫,汤雪明,李慧.骨折Ⅱ期愈合过程中的成纤维细胞成骨[J].中华骨科杂志,1996,16：245.
[58]史炜镔,符诗聪,杜宁,等.丹参有效部位对骨折愈合过程中胶原基因表达的影响[J].中国中西医结合杂志,2000,20(4)：269.
[59]秦军志.丹参对大鼠胫骨骨折早期愈合过程中血清、骨痂及骨组织中钙、锌、铜的影响[J].中国中西医结合杂志,1992,12(6)：354.
[60]贺旭峰,沈强.丹参及其相关制剂对促进骨折愈合的国内研究进展[J].中国骨伤,2007,20(6)：426～427.
[61]赵晓莲,翟饶生,李晶,等.红花对家兔实验性骨折愈合中锌铜含量的影响[J].黑龙江医药科学,2004,27(2)：43.
[62]崔永锋,张永斌,李刚,等.杜仲对兔骨折愈合影响的光镜观察实验研究[J].中国比较医学杂志,2005,15(3)：154.
[63]郑军,董福慧,程伟.水蛙对骨愈合相关基因表达影响[J].中国骨伤,2003,16(9)：513.
[64]王华松,黄琼霞,许申明.骨碎补对骨折愈合中血生化指TGF-β1表达的影响[J].中医正骨,2001,13(5)：6.
[65]鲍善芬,赵霖,刘玉杰,等.金属铜对骨折愈合作用的实验研究[J].中华外科杂志,2002,40(7)：538.
[66]程志安,吴燕峰,黄智清,等.续断对成骨细胞增殖、分化、凋亡和细胞周期的影响[J].中医正骨,2004,16(12)：1.
[67]侯晓峰,李朝旭,刘景生.鹿茸对实验型骨折愈合中BMP-2表达的影响.辽宁中医杂志[J],2005,32(4)：374.
[70]高云,董福慧,郑军.海螵蛸对骨愈合相关基因表达的影响[J].中医正骨,2004,16(7)：1.
[71]张国文,李晓玲.中药中7种微量元素的测定[J].微量元素与健康研究,1998,15(2)：44.
[72]覃旭.马钱子促进骨折愈合的研究进展[J].贵阳中医学院学报,2006,29(2)：67.
[72]陆炳全,黄素碧,贺景国等.自然铜促进骨折愈合实验研究[J].中外健康文摘,2006,3(9)：77.
[73]周琦百,黄枫,郑晓辉.补肾接骨口服液促进骨折愈合60例疗效观察[J].中国中医骨伤科杂志,2005,6(3)：31～33.
[74]张治国,崔大领.“张氏接骨散’,促进骨折愈合的临床观察[J].中医药研究,1995,15(5)：9.
[75]朱以锦.化痰祛瘀补肾治疗股骨颈骨折延迟愈合30例[J].四川中医,2002,20(12)：63.
[75]蒋顺琬,杨卓欣,林志文.壮筋补骨丸促进骨折愈合的临床研究[J].广州中医药大学学报,2004,2(15)：373.
[76]田玉环,付爱平,刘国胜.正奇接骨丹颗粒剂治疗创伤骨折临床研究[J].中国实验方剂学杂志,2004,10(4)：61.
[77]高锦麟,许祥生.消肿接骨糖浆治疗骨折319例临床观察[J].陕西中医学院学报,1994,17(2)：181.
[78]白礼河,白理智,董引娣,等.生骨散促进骨折愈合作用的临床观察[J].中医正骨,1995,7(3)：101.
[79]刘滨生.中药生肌散治疗开放性骨折合并软组织缺损的疗效观察[J].中医药学报,2002,30(4)：37.
[80]汤耿民,王胜利,王和鸣,等.三花接骨散促进骨折愈合临床实验研究[J].中国中医骨伤科杂志[J],1995,3(3)：161[81]陈晋杰,潘少川,张连柱,等.三花接骨散治疗骨折的实验性报告[J].北京医学,1995,17(1)：581.
[82]匡建华.接骨理伤汤促进骨折愈合50例[J].湖南中医杂志,2003,5,19(3)：19.
[83]吴官保.跌打促愈片治疗胫腓骨骨折46例[J].湖南中医杂志,2002,7,18(4)：13.
[84]贾恩礼.中药“生骨胶囊”治疗骨折及股骨头坏死的临床效果[J].实用医药杂志,2002,10,19(10)：778～779.
[85]张越林,牛惠敏.中药治疗骨折延迟愈合的临床观察[J].天津中医,1996,13(2)：241.
[86]任桂兰.阳和汤合剂治疗骨折延迟连接疗效观察[J].中医正骨,1999,11(2)：111.
[87]谭德雄.金锁固精丸治疗骨折迟缓愈合22例报告[J].中国中医骨伤科杂志,1991,7(2)：441.
[88]郑祖纯.白蛤健骨丸治疗骨折迟缓愈合147例[J].内蒙古中医药,1993,(4)：51.
[89]杨海韵,陈逊文,陈志维,等.“骨宝丸”促进骨折愈合作用的临床疗效观察和实验研究[J].中国中西医结合外科杂志,1996,3：203-205.
[90]周成刚.正骨丹促进骨折愈合疗效观察[J].中国中医骨伤科杂志,2003,11(1)：19.21.
[91]陈玲,杨云洲,陈继革,等.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[92]沈祥春,张贵林,任光友,等.抗骨折方促进实验性大鼠骨折愈合作用的研究[J].中华中医药杂志,2007,22(5)：285-288.
[93]王银环,韩淑英,朱丽莎,等.双黄冲剂对兔骨折愈合的实验研究[J].华北煤炭医学院学报,2008,10(5)：585～586.
[94]卞俊,陈海飞,宣伟东等.愈骨疗伤胶囊促进骨折愈合的药效学实验[J].中成药[J],2008,30(11)：1682.
[95]陈世同.挫伤接骨膏治疗创伤骨折555例临床总结[J].江苏中医,1990,11(9)：221.
[96]杨力.接骨膏对骨折愈合作用的探讨[J].河北中医,1995：17(4)：271.
[97]孙炳烈,赵然,王梦娟等.明氏外用接骨膏促进骨折愈合的实验研究[J].中国中医骨伤科杂志,1990,6(4)：4.
[98]焦志国.生骨丹外敷内服治疗骨折延迟愈合和骨不连的疗效分析[J].中国现代药物 应用,2009,3(10)：131.
[99]侯莜魁,石关桐,赵敏辉等.外敷中药对家兔桡骨骨折愈合的影响[J].中国中医骨伤科杂志,1992,13(2)：10.
[100]谢明夫,苏庆洋,刘丽清.外用“接骨散”治疗四肢骨折迟缓愈合25例[J].菏泽医学专报,1999,11(1)：62.
[101]袁昌锦,付天明,刘敏等.中草药接骨膏对家兔创伤性骨折愈合作用的实验研究[J].四川中医,2005,23(10)：34-36.
[102]江树连,丁锷,李保泉.消瘀接骨散外敷对家兔骨折愈合影响的实验研究[J].中医外治杂志,2000,9(3)：34～36.
[103]张建国.活血消肿接骨散对兔骨折愈合骨痂强度的影响[J].中医正骨,2002,14(9)：522～523.
[104]翟献斌,王宗辉.泰山接骨膏治疗骨折的临床研究[J].中医正骨,2007,19(4)：11～12.
[105]陶志东,孙成长,毛伟欢.消肿散瘀膏外敷治疗骨折158例[J].山东中医杂志,2009,28(9)：11～12.
[106]熊芳丽,肖亚平,针灸促进骨折愈合的临床观察.中国针灸,1997,17(11)：6851.
[107]邹志军,张建军,马凤英,等.巨刺疗法对股骨颈骨折延迟愈合的疗效观察.中国中医骨伤科杂志,1991,7(3)：321.
[108]张作君,赵然,成传德,等.针刺、艾灸促进骨折愈合的实验研究[J].中医正骨,1992,4(2)：71.
[109]刘滨生.前臂骨折后期的辅助针刺疗法[J].针灸临床杂志,2002,18(6)：16.
[110]李心沁,王琳,单秋华.针刺对大鼠骨折愈合及骨痂TGF-β1表达的影响[J].山东中医杂志,2006,25(8)：546～548.
[111]刘家瑞.穴位注射配合物理疗法治疗胸腰椎压缩性骨折[J].中国康复,2006,21(3)：198.
[112]周黎明.电针治疗胫骨骨折迟缓愈合52例疗效观察[J].中国针灸,2000(10)：599-600.
[113]王全权,陈海林,张兴国.穴位注射结合中药促进尺桡骨骨折愈合的疗效观察[J].成都中医药大学学报,2005,28(2)：23-24.
[114]卢敏,谢进,戴致波.小针刀对兔骨折愈合影响的实验研究[J].湖南中医药大学学报,2007,27(4)：70～72.
[115]卢敏,戴致波,谢进.小针刀治疗对骨折愈合血管内皮细胞生长因子表达及血清无机盐和碱性磷酸酶影响的实验研究[J].中国中医骨伤科杂志,2007,15(6)：9-11.
[116]孙维琰,黎君若,王素芳,等.中药电热夹板促进骨折愈合的临床研究[J].中国中医骨伤科杂志,1991,7(4)：121.
[117]孙炳烈,郭建刚,赵然,等.中药电热夹板促进骨折愈合的实验研究.中国中医骨伤科杂志,1991,7(4)：151.
[1]邹声泉,龚建平.外科学-前沿与争论[M].北京：人民卫生出版社.2003,815-836.
[2]Issack PS, Di sesare PE. Recent advances toward the Clinical application of bone morphogenetic proteins in bone and repair. Am J Orthop. Am J Orthop[J].2003,32 (9): 429-436.
[3]Szczesny G. Growth factors in bone. Int Orthop[J].1998,22 (6):410-416.
[4]Chen D, Harris MA. BMP-2 enhances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation in cultures of fetal rat calvarial osteoblasts[J].. Calcif TissueInt,1997,60(3):283.
[5]Onishi T, Ishidou Y, Nagamine T, et al. Distinct and over lapping patterns of localization of bone morphogenetic protein family members and a BMP type Ⅱ receptor during fracture healing in rat s. Bone,1998,22:605.
[6]曾中华,余黎,龚玲玲,等.骨折愈合过程中BMP-2和VEGF的表达[J].武汉大学学报.2005,26(4)：467～469.
[7]朱六龙,戴克戎.骨形成蛋白22基因转染人骨髓间质干细胞诱导异位成骨的实验研究[J].中国修复重建外科杂志.2003,17(2)：131—135.
[8]尹战海,王坤正,张沈荣,等.骨形成蛋白增强自体骨修复股骨头骨缺损的研究[J].中国修复重建外科杂志,2002,16(2)：93-96.
[9]ZabkaAG, PluharGE, Edwards RB 3rd, et al. Histomorphometric descriptin of allograft bone remodeling and union in a canine segmental femoral defect model:a comparison of rhBMP-2, cancellous bone, and absorbable collagen sponge[J]. J Orthop Res,2001, 19(2):318—327.
[10]Rnhe PQ, Kroese-Deutman HC, wolke JG, et al. Bone inductive properties of rhBMP-2 loaded po rous calcium phosphate cement implants incranial defects in rabbits[J]. Biomaterials,2004,25(11):2123—2132.
[11]杜俊杰,等.p转化生长因子增强人重组骨形发生蛋白-2诱导成骨的调节机理[J].中国矫形外科杂志,1998,(5),6：536.
[12]Maliakal JC, Asahina I, Hauschika PV et al. Osteogenic protein-7(BMP-7)inhibits cell proliferation stimulates the expression of makers characteristic of osteoblast phenotype in rat osteosarcoma cells[J]. Growth Factors,1994;11 (3):227.
[13]张永刚,卢世璧,王继芳.骨引导与骨诱导[J].中华创伤杂志,1996,31(1)：1992209.
[14]Okubo Y. BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest[J]. Development,2000,2962(5):109521104.
[15]Sakou T. Bone morphogenetic proteins:from basic studies to clinical approaches[J]. Bone,1998,22 (6):5912603.
[16]Dragoo. Newest factors in fracture healing[J]. Clin Orthop,1992,27 (7):297-311.
[17]A st rom A K, J in D, Imamura T, et al. Current concepts growth factors in bone[J]. IntOrthopedics,1998 (22):410-416.
[18]Chen D, Harris MA. BMP-2 enchances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation in cultures of fetal tat calvarial osteo blasts[J]. Calcif Tissue Int (inpress),2003, (12):2102216.
[19]刘健,胡蕴玉,马真胜,等.骨折愈合过程中BMP-3基因表达的实验研究[J]中华外科杂志,1996,34(10)：585-587.
[20]Ghosh-Choudhury N, Harris MA,Chen D,et al. Transfection of BMP-2 expression plasmial induces osteoblastic differentiation in a BMP-2 dependent preosteoblast cell line[J].J Bone Miner Res,2004,9(suppl1):137.
[21]Stone CA. Amo lecular approach to bone regeneration[J]. British J Plastic Surgery,2003, 50(5):369-373.
[22]Reddi A H. Morphogenes is and tissue engineering of bone andcartilage:inductive signals, stem cells,and biomimetic bioma-terials[J]. Tissue Eng,2000,6 (4):351-359.
[23]张子军,卢世璧,王继芳,等.骨缺损中内源性BMP的分布及其作用[J].中华外科杂志,1996,34(10)：596-597.
[24]Kubler N, Urist MR. Clin orthop.1998,292:321-328.
[25]Miyamoto S, Takaoka K etal. Calcif Tissue Int,1992,50(suppl1):15.
[26]Reddi AH. Bone morphogenetic proteins, bone marrow stromal cells, and mesenchymal stem cells. Clin Orthop,200,313):115-119.
[27]Einhorn TA, Majeska RJ, Mohaideen A, et al. A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair[J]. J Bone Joint Surg Am,200385-A (8):1425-1435.
[28]Sheehan JP, Sheehan JM, Sheehan JM H, et al.The safety and utility of recombinant human bone morphogenetic protein-2 for cranial procedures in a nonhuman primate model.[J].J Neursurg,2003,98 (1):125-130.
[29]苏佳灿,许硕贵,张春才.生长因子与骨重建研究进展[J].临床骨科杂志,2001,4(2)：155.
[30]Yee JA, Yan L, Domin JC etal. Plasminogen dependent activation of latent transforming growth factor beta by growing cultures of osteoblast-like cells[J]. J Cell Physiol,1993, 157(5):528-534.
[31]Oreffo RO, Bonewald L, Kukita A et al. Inhibitory effects of the bone-derived growth factors osteoinductive factor and transforming growth factor-beta on iso-lated osteoclasts [J].Endocrinology,1990,126 (10):69～75.
[32]Bolander ME. Regulation of fracture repair by growth factors[J]. Proc Soc ExpBiol Med, 1992,200(2):165～170.
[33]Joyce ME, Terek RM, Jingushi S et al. Role of transforming growth factor-betain fracture healing [J].Ann N Y AcadSci,1990,593 (1):107～123.
[34]Sandberg MM, Aro HT, Vuorio EL etal. Gene expression during fracture repair[J]. Clin Orthop,1993, (289):292～312.
[35]Shuto T, Sarkar G, Bronk J T et al. Osteoblasts express type Ⅰ and Ⅱ activin receptors during early intramembranous and endochondral bone formation [J] JBone Miner Res, 1997,12(3):403～411.
[36]Whitman M. Feedback from inhibitory SMADs[J].Nature,1997,389 (4):549～551.
[37]Beck LS, Deguzman L, Wyne LP et al. TGF-beta-2 induces bone closure of skull defects [J]. J Bone Miner Res,1991,6 (8):1257～1265.
[38]Critchlow MA, Bland YS, Ashahurst DE et al. The effects of age on the response of rabbit periosteal osteoprogenitor cells to exogenous transforming growth factor beta-2[J]. J Cell Sci,1994,107(4):499～516.
[39]Nielsen HM, Andreassen TT, Ledet T et al. Local injection of TGF-beta increases the strength of tibial fractures in the rat [J]. Acta Orthop Scand,1994,65 (1):37～41.
[40]Lind M, Overgaard S, Nguyen T et al. Transforming growth factor2beta stimulates bone ongrowth:hydroxyapatitecoated implants study in dogs [J]. Acta Orthop Scand,1996, 67(5):611～616.
[41]Joyce ME, RobertsAB, SporeMB, et al. Transforming growthfactor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur[J]. J Cell Biol,1990,110(6): 2195-2207.
[42]田卫东,王大章.生长因子网络调节对骨形成作用的研究[J].华西口腔医学杂志,1998,16(2)：65～72.
[43]Farhadieh RD, Dickinson R, Yu Y, et al. The role of transforming growth factor-beta, insulin-like growth factor I, and basic fibroblast growth factor in distraction osteogenesis of the mandible[J]. J Craniofac Surg,1999,10:80.
[44]田卫东,王大章,乔鞠,等.生长因子网络调节对骨形成作用的研究：bFGF对人胚成骨样细胞增殖及分化的影响[J].华西口腔医学杂志,1998,16(4)：344～347.
[45]龚振字,周树夏,曹建广,等.碱性成纤维细胞生长因子对兔下颌骨骨折愈合中细胞增殖的影响[J].实用口腔医学杂志,2007,11(5)：385～387.
[46]Amizuka N, Davidson D, Liu H, et al. Signalling by fibroblast growth factor receptor 3 and parathyroid hormone-related peptide coordinate cartilageand bone development[J]. Bone,2004,34(1):13～25.
[47]Walsh S, Jeferiss C, Stewart K, et al. Expression of the developmental makers STRO-1 and alkaline phosphatase in cultures of hunman marrow stromal cells:regulation by fibroblast growth factor(FGF)-2 and relationship to the expression of FGF receptors 1-4[J]. Bone,2000,27(2):185～195.
[48]Globus RK, Pat terson2Buckendahl P, Gospodarowicz D1 Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta[J]. Endocrinology,1988,123:98～1051.
[49]Canalis E, Cent rella M, McCart hy T. Effect of basic fibroblast factor on bone formation in vitro [J]. J Clin Invest,1988,81:1572～1577.
[50]Iwasaki M, Nakahara H, Nakata K, et al. Regulation of proliferation and osteochondrogenic differentiation of periosteumderived cells by transforming growth factor beta and basic fibroblast growth factor [J]. J Bone Joint Surg (Am),1995, 77:543-554.
[51]Kawaguchi H, Kurokawa T, Hanada K, et al. Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin2diabetic rats. Endocrinology,1994,135:774-781.
[52]王立平,党耕町.碱性成纤维细胞生长因子在骨愈合过程中的表达与合成[J].中华骨科杂志,1999,19(8)：488～490.
[53]Baddoo M, Hill K, Wilkinson R, et al. Characterization of mesenchymal stem cells isolation from murine bone marrow by negative selection[J]. J Cell Biochem,2003, 89:1235～1249.
[54]Lisignoli G, Fini M, Giavaresi G, et al. Osteogenesis of large segmental radius defects enhanced by basic fibroblast growth factor actirated bone marrow stromal cells grown on non-woven hyaluronic acid-based polymer scaffold[J]. Biomaterials,2002, 23:1043～1051.
[55]Schmal H, Mehlhorn A T, Fehrenbach M, et al. Regulative mechanisms of chondrocyte adhesion [J]. Tissue Eng,2006,12:741～750.
[56]Wong W C, Yu X, Wallace A L, et al. Use of a polymeric device to deliver growth factors to a healing fracture [J]. ANZ J Surg,2003,73:1022～1027.
[57]Pacicca DM, Patel N, Lee C, et al. Expression of angiogenic factors during distraction osteogenesis[J]. Bone,2003,33:889～898.
[58]Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in t he regula2tion of osteoblast function and bone growt h[J] Development,2003,130:306323074.
[59]Clarke S A, Brooks R A, Lee P T, et al. The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant [J]. J Ort hop Res,2004, 22:1016～1024.
[60]Kawaguchi H, Nakamura K, Tabata Y, et al. Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2[J]. J Clin Endocrinol Metab,2001, 86:875～880.
[61]Kawaguchi H, Nakamura K, Tabata Y, et al. Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2 [J]. J Clin Endocrinol Metab,2001, 86:875～880.
[62]Montero A, Okada Y, Tomita M, et al. Disruption of the fibroblast growth factor-2 gene result s in decreased bone mass and bone formation[J]. J Clin Invest,2000, 105:1085～1093.
[63]Debiais F, Lefevre G, Lemonnier J. Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3-ki-nase-dependent,beta-catenin-independent signaling pathway[J].Exp Cell Res,2004,297:235-246.
[64]Fukuda A, Kato K, Hasegawa M, et al. Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast factor [J]. Biomaterial s, 2005,26:4301-4308.
[65]Linkhant TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair:IGF, TGFβand BMP[J]. Bone,1996,19:1. [66] Kanzaki S, Hilliker S, Baylink DJ, et al. Evidence that HBC in culture produce IGFBP-4 and-5 proteases [J]. Endocronology, 1994,134:383.
[67]Brown DJ, kaoWW, Greenhalgh DG. apoptosis down-regulates inflame mation under the advancing ep ithelial wound edge:delayed patterns indiabetes and improvement with topical growth factors [J]. Surgery,1997,12 (14):372.
[68]Shenaq SM, Rabinovsky ED. Gene therapy for plastic and reconstructive surgery J [J]. Clin Plast Surg,1996,23 (1):157.
[69]JeschkeM G, Barrow R E, Hawkins H K. Effect of multiple gene transfers of in sulin like growth factor I complementary DNA gene constructs in rats after thermal injury[J]. Arch Surg,1999,134(10):1137.
[70]Eming SA, Lee J, Snow Rg, et al. Genetically modified human epidermis over-expressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice:implications for the use of genetically modified keratinocytes tomodulate dermal regeneration[J]. J Invest Dermatol,1995,105:756.
[71]吉建新,廖伟娇,邱志辉,等.碱性成纤维细胞生长因子和胰岛素样生长因子-1对牙周膜细胞增殖的影响[J].广州医药杂志,2005,26(5)：606
[72]Andrew JG, Hoyland J, Freemont AJ, et al. Insulin-like growth factor gene expression in human fracture callus[J]. Calcif Tissue Int,1993,53(2):97.
[73]McCarthy TL, J i C, Casinghino S, et al. Alternate signaling pathways selectively regulate binding of insulin-like growth factor Ⅰ and Ⅱ on fetal rat bone cells[J] J. Cell Biochem,1998,68 (4):446.
[74]Murphy Mg, Bach MA, Plotkin D, et al. Oral administra-tion of the growth hormone secretagogue MK-677 in-creases markers of bone turnover inhealthy and functional-ly impaired elderly adults. TheMK-677 Study Group [J]. J BoneMiner Res,1999,14 (7):1182.
[75]李亚非,李青,马福成.人骨折骨痂中胰岛素样生长因子Ⅰ的免疫组化研究[J].中华实验外科杂志,1997,14(3)：191.
[76]王振海,付勤,赵忠海.EGF和IGF对体外培养兔关节软骨细胞的影响[J].中国骨伤,2003,16(1)：23.
[77]刘刚,胡蕴玉,马平,等.胰岛素样生长因子-Ⅰ对兔关节软骨细胞增殖及代谢的影响[J].中国修复重建外科杂志,2002,16(4)：228.
[78]Kudo-Y, Iwashita-M, iguchi-T, et al. The regulation of type-1 collagen synthesis by insulin-like growth factor-1 in human osteoblast-like SaOS-2 cells[J]. P flugers-Aarch, 1996,433 (1-2):123.
[79]Ferrara N, Henzel WJ. P ituitary Fo llicular cell secrete a novel heparin-binding growth factor specific for vascular endo thelial cells [J]. Biochem Biophys Res Commun,1989; 161 (2):8512858.
[80]Conno lly DT, Heuvel man DM, N elson R. et al. Tumor Vascular permeablility factor stimulates endothelial cell growth and angio lgenesis [J]. J Clin Invest,1989; 84: 1470～1478.
[81]Street JT, W ang JH, W u QD, et al. The angiogenic response to skeletal injury is p reserved in the elderly[J]. J O rthop R es,2001,19 (6):1057～1066.
[82]Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor. an endothelial cell mitogen related to PDGF [J]. S cience,1989,246:1309～1312.
[83]Homer A, B ishop NJ, Bo rd S, et al. Immune localisation of vascular endo thelial growth factor (VEGF) in human neonatal growth plate cartilage[J]. J A nat,1999; 194 (4): 519-524.
[84]Pufe T, Peterson W, T illmann B, et al. The angiogenic peptide vascular endo thelial growth factor is expressed in foetal and ruptured tendons [J]. J V irchow s A rch,2001; 439 (4):579～585.
[85]Gerstenfeld LC, Cullinance DM, Barnes GL, et al. Fracture healing as a post-natal developmental process:molecular spatial and temporal aspects of its regulation [J]. J Cell Biochem,2003; 88 (5):873～884.
[86]Hayam i T, Funaki H, Yaoeda K. Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis [J]. J R heum atol,2003; 30(10):2207～2217.
[87]钟刚,裴福兴,樊瑜波,等.V EGF基因转染促进骨折愈合的实验研究[J].中国矫形外科杂志,2004；12(8)：604～609.
[88]杨操,杨述华,杜靖远,等.V EGF基因转染促进股骨头坏死修复[J].临床骨科杂志,2004；7(1)：90～93.
[89]初同伟,王正国,朱佩芳,等.骨折愈合过程中血流量的变化与VEGF的相关性研究[J].中国矫形外科杂志,2002；9(6)：577～579.
[90]Street J, Bao M, Guzman L, et al. Vascularendo thelial growth stimulates bone repair buromo ting angiogenesis and bone turnover [J]. Proc Natl Acad Sci USA,2002; 99 (15):9656～9661.
[91]Peng H, W right V, U sas A, et al. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4[J]. J C lin Inv est,2000; 110 (6):751～759.
[92]M usch ler GF, N akamo to C, Griffith L G, et al. Engineering principles of clinical cell-based tissue engineering [J]. J B one Joint Surg A m,2004,86-A (7):1541～1558.
[93]Lattermann C, Baltzer AW, Zelle BA, et al. Feasibility of percutaneous gene transfer to anatrophic nonunion in a rabbit [J]. J orthop Res,2004,425 (8):237-243.
[94]刘日光,尹培荣,杨述华,等.人VEGF 165基因在狗脊髓细胞中的表达[J].中国矫形外科杂志,2004,12(19)：1476～1478.
[95]杨述华,杨操,许伟华,等.人血管内皮生长因子的cDNA克隆及其在兔成骨细胞中的表达[J].中华骨科杂志,2002；20(2)：99～102.
[96]王代友,于大海,邝晓聪,等.人血管内皮生长因子基因的克隆及其真核表达质粒的构建[J].广西医科大学学报,2004,21(1)：8-10.
[97]初同伟,王正国,朱佩芳,等.骨折愈合过程中VEGF及其受体的表达[J].中华创伤杂志,2001,17(6)：344～346.
[98]刘杰,孙正义,曹蕾,等.血管内皮生长因子对生物衍生骨复合骨髓基质细胞体内成骨的影响[J].中国临床康复,2003,7(11)：1622～1623.
[99]钟刚,裴福兴,樊瑜波,等.VEGF基因转染促进骨折愈合的实验研究[J].中国矫形外科杂志,2004,12(8)：604～609.
[100]鱼兵,闫露,范清宇,等.人BMP-7及VEGF 165基因共表达腺病毒的构建及在兔骨髓基质干细胞中的共表达[J].中国矫形外科杂志,2004,12(21-22)：1704～1707.
[1]柴本甫,过邦辅.理气药物对骨折愈合的影响的初步研究.中华外科杂志,1962,10(5)：299.
[2]李光辉,陈超.伤科接骨片对家兔骨折后血液流变性的影响[J].中国中医急症,2003,12(1)：61.
[3]陈玲,杨云洲,陈继革.接骨七厘片促进大鼠骨折愈合的实验研究[J].湖北中医杂志,2005,27(1)：50～52.
[4]张金海,张伟成.补肾活血合剂促进骨折愈合的实验研究[J].现代中西医结合杂志,2007,16(10)：1321～1322.
[5]刘进.张雪华.氟化钠、自然铜、维生素C成骨效果的实验研究[J].临床口腔医学杂志,1997,13(4)：224.
[6]张克勤,刘湘秀,李瑞宗.七厘散对骨折愈合作用的初步实验研究[J].中华外科杂志,1962,10(5)：305.
[7]毛弋平.谈自然铜炮制方法[J].现代应用药学,1994.11(3)：17.
[8]王静,毛春芹,陆兔林,等.中药醋制法研究进展[J]中国中医药信息杂志,2009,16(1)99-101.
[9]张冒颖.生物化学[M].北京：人民卫生出版社,1987.589.
[10]薛少汀,葛宝丰,徐印坎,等.实用骨科学[M],北京：人民军医出版社.2005,29.
[11]北京医学院主编.生物化学[M].北京：人民卫生出版社,1978.497-498.
[12]董华,胡乃武,董清平,等.骨痛仙胶囊对家兔骨折血清碱性磷酸酶、钙、磷影响的实验研究[J].中医药学报,2003,2(31)：51-52.
[13]袁强,志文,张爱国,等.麝香乌龙丸对兔实验骨折Ca、P、ALP的作用研究[J].陕西中医,2006,27(11)：1443-1442.
[14]周晶亚.中草药接骨膏促进骨折愈合作用的实验研究[J].时珍国医国药,2008,19(8)：2014～2015.
[15]林军,王慧明,曹之强,等.下颌骨缺损修复过程中Ⅰ型胶原基因表达的实验研究[J].中国口腔种植医学杂志,2001,6(1)：7-10.
[16]曾岩,马庆军,郭昭庆,等.骨髓基质细胞体外培养成骨能力的实验研究[J].中华骨科杂志,2001,21(1)：45～49.
[17]Robert s AB, Sporn MB, Assion RK, et al. Transforming growth factor2β:rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA[J],1986,81(4):167.
[18]Chen D, Harris MA.BMP-2 enhances BMP-3, BMP-4 and bone cell differentiation marker genes expression during the induction of mineralizal bone matrix formation incultures of fetal rat calvarial osteoblasts. Calcif Tissue Int[J],1997,60 (3):283.
[19]Onishi T, Ishidou Y, Nagamine T, et al. Distinct and over lapping patternsof localization of bone morphogenetic protein family members and a BMP type Ⅱ receptor during fracture healing in rats. Bone[J],1998,22:605.
[20]韩立军,王俊红,孙建国,等.中药治疗骨折的两阶段学说及临床研究.河北中医药学报,2000,15(1)：12～14.