补肾活血法对关节骨折术后软骨退变相关因子及功能康复的影响
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摘要
创伤性关节炎(Post-traumatic Osteoarthritis)是继发于关节创伤的骨关节炎,是由于连续的物理性或机械性损伤导致的可运动关节的软骨变性、破坏,以及在此基础上的关节软骨、软骨下骨、滑膜、关节囊及周围的肌肉和韧带的一系列改变而引起的关节功能障碍。
近年来,随着高能量损伤致关节软骨损伤的机率增大,创伤性关节炎的发病率呈现逐年增加的趋势。因其临床主要表现为受累关节的疼痛、不同程度的关节活动障碍,严重者有畸形改变,甚至致残,后果严峻：因此一直是临床治疗关注的焦点和难点。
研究目的
通过临床研究和动物实验,探讨运用补肾活血方药辨证施治用药,能否有效影响关节骨折术后的关节软骨退变相关因子；能否从整体上对关节骨折术后患者产生调理,促进关节骨折术后患者关节功能的康复过程,提高疗效。
研究内容和方法
采用临床研究及动物实验研究。
临床研究
临床资料及方法：选取临床收治涉膝关节关节面的高能量损伤骨折并进行内固定术后患者约60人,设补肾活血组、西乐葆组和空白组。另从健康志愿者中选取20人作为正常对照组。补肾活血组予以活血补肾方汤剂口服。
临床研究一：于术后1周、3周及8周,进行血清和关节液TNF-a、MMP-3和NO浓度检测。
临床研究二：术后3周和8周,通过对相关症状、体征及中医证候进行综合计分来进行疗效评价。
动物实验研究
选择成年雄性SD大鼠40只采用完全随机设计,分成正常组,补肾活血组,西乐葆组和空白组,每组10只。术后3天,7天及21天进行血清和关节液TNF-a、MMP-3和NO浓度检测。
研究结果
通过临床研究,我们发现,各组1周、3周和8周TNF-a和NO水平有逐渐升高趋势,两两比较均有显著性差异。而各组3周到8周的血清及关节液TNF-a水平间存在相关关系。说明这期间MMP-3的升高与TNF-a水平增高相关。同时,在3周和8周的对比中,空白组关节液和血清TNF-a、MMP-3和NO的水平均显著高于补肾活血组。说明应用补肾活血法的补肾活血组对这期间的TNF-a、MMP-3和NO的水平增长能有效抑制。
临床疗效评价：3周时功能计分和总计分,三组患者的计分均无显著性差异(P>0.05),说明3周时三组患者病情具有可比性。8周时三组患者所有项目计分均较3周时改善(P<0.05)。疼痛计分,西乐葆组均显著高于其他两组(P<0.05),而补肾活血组在8周时优于空白组(P<0.05)。8周时三组患者的总计分和功能计分比较,补肾活血组和西乐葆组差异均无显著性意义(P>0.05)；但优于空白组(P<0.05)。中医证候计分比较,补肾活血组均显著高于其他两组(P<0.05)。疾病疗效比较补肾活血组与西乐葆组的疾病疗效相仿(P>0.05),而空白组较两组低(P<0.05)。补肾活血组的中医证候疗效高于西乐葆组和空白组(P<0.05)。
动物实验研究显示,补肾活血组在抑制血清TNF-a、MMP-3及NO等水平升高方面明显优于空白对照组。各组TNF-a、MMP-3及NO水平变化进程和临床实验研究结果相近。
研究结论
在本研究中,辨证认为关节骨折术后的关节软骨退变,多以肝肾不足为本,气滞血瘀为标。故针对此病机证候,治法应以补肾活血为主。同时,根据术后具体病机证候变化,辨证用药,适当加减。术后早期,气滞血瘀证为主,肝肾不足为次,因此治疗以加强活血祛瘀之方药,以消肿止痛,行气和营。中后期,则以肝肾不足为主,气滞血瘀之证为次。故治疗以补肾养肝为重而兼以活血行气之功。
通过临床和动物实验室检验结果证实,补肾活血组对关节骨折固定术后的TNF-a、MMP-3和NO水平增长能有效抑制；证明运用补肾活血方药辨证施治用药,能有效防治关节骨折术后的关节软骨退变进程。
而根据临床观察研究结果,应用补肾活血法的补肾活血组,在关节骨折创伤术后的疼痛控制,功能恢复方面和临床常用药物西乐葆的功效相近,而优于空白对照组。同时,补肾活血法在治疗中医证候方面疗效明显。因此可证实,补肾活血法能有效防治关节骨折创伤术后关节软骨退变进展,缓解疼痛和促进功能恢复,提高临床治疗和康复的疗效。
综上所述,根据研究实验结果,可以证实：运用补肾活血方药辨证施治用药,能有效影响关节骨折术后的团结软骨退变相关因子。补肾活血法能从整体上对关节骨折术后患者产生调理,促进关节骨折术后患者关节功能的康复过程,提高疗效。
由此,研究结论认为补肾活血法在对于抑制关节骨折后关节软骨退变的进程,并促进关节骨折术后患者关节功能的康复方面,产生积极和有利的影响。
Post-traumatic Osteoarthritis is a kind of osteoarthritis resulting from joint trauma and a kind of joint dysfunction resulting from cartilage denaturalization and destruction in movable joints due to continuous physical or mechanical damages and from the subsequent changes in articular cartilage, subchondral bone, synovium, joint capsule and surrounding muscles and ligaments.
In recent years, with the increase of the probability of high energy traumas caused by articular cartilage injury, the incidence rate of the Post-traumatic Osteoarthritis has been rising year by year. Its main clinical features include the pain in involved joints, joint movement disorder in different degrees and even malformation or disability, which has made it a focus and difficulty in clinical treatment.
Objective
Through clinical studies and animal experiments, discuss whether using invigorating kidney and promoting blood flow treament of syndrome differentiation can effectively prevent and control the pathological change process of cartilage cataplasia after the articular fracture operations, can promote the healing process of the joint function of the patients after the articular fracture operations for a better curative effect and can have overall conditioning and rehabilitation effects on the patients after the articular fracture operations for a better quality of life.
Methods
Clinical Study and Animal Experiments are adopted.
Clinical Study
Clinical data and methods:Choose about 60 patients suffering from high-energy post-traumatic fracture involved with knee and ankle joints' articular surfaces, who have go through the internal fixation operations, to set up a treatment group, a Celebrex group and a blank group. And choose 20 non-fracture patients to set up a normal control group. The treatment group will take the oral medication of invigorating kidney and promoting blood flow treament.
Clinical Study 1:In the 1st,3rd and 8th weeks after operation, measure the TNF-a, MMP-3 and NO concentrations in terms of serum and synovial fluid.
Clinical Study 2:Three weeks and eight weeks after operation, evaluate the curative effect by means of overall scoring on the related symptoms, physical signs and TCM symptoms.
Animal Experiments
Choose 40 adult male SD rats and divide them into a normal group, a treatment group, a Celebrex group and a blank group by means of completely random design, with 10 in each group. On the 3rd,7th and 21st days after operation, measure the TNF-a, MMP-3 and NO concentrations in terms of serum and synovial fluid.
Results
Through the clinical study, we have found out that there is a gradual increase in the TNF-a and NO concentrations in each group on the 1st,3rd and 8th weeks after operation, with significant deviation between each two groups. However, the TNF-a levels of the serum and of the synovial fluid in each group are correlated in the 3-8 weeks. This shows that the increase of MMP-3 is related to that of the TNF-a level during this period. In the meantime, when comparing the data of the 3rd week with that of the 8th week, the TNF-a, MMP-3 and NO levels of the blank group in terms of serum and synovial fluid are all much higher than that of the treatment group. This shows that the treatment group adopting invigorating kidney and promoting blood flow treament can effectively control the increase of the TNF-a, MMP-3 and NO levels during this period.
Clinical Effect Evaluation:With reference to the function scoring and total scoring, there are little difference among the scorings of all the three groups (P> 0.05), which shows that the three groups'illness is comparable in the 3rd week. All the scorings of the three groups in the 8th week are better than that in the 3rd week (P<0.05). In terms of pain scoring, the Celebrex group are much better than the other two groups (P<0.05), while the treatment group exceeds the blank group in the 8th week (P<0.05). Judging from the comparison between the total scorings and function scorings of the three groups in the 8th week, the difference in the treatment group and the Celebrex group are of no significance (P>0.05); but they are better than the blank group (P<0.05). In terms of TCM symptom scoring, the treatment group's scores are all higher than that of the other two groups (P<0.05). As to the curative effects, the treatment group is similar to the Celebrex group (P>0.05), both better than the blank group (P<0.05). The treatment group is better than the Celebrex group and the blank group in terms of the curative effects on TCM symptoms (P<0.05).
The animal experiments show that the treatment group is much better than the blank group in terms of the control of the increase of the TNF-a, MMP-3 and NO levels of serum. The changing process of each group's TNF-a, MMP-3 and NO levels is close to the results of the clinical experiments. Conclusion
In this research, syndrome differentiation shows that the Post-traumatic Osteoarthritis occurring after the articular fracture operation is generally based on the liver and kidney deficiency with qi stagnation and blood stasis as the standard. Therefore, invigorating kidney and promoting blood flow treament is the prevailing therapy. Meanwhile, according to the changes in specific symptoms after operation, adopt syndrome differentiation with appropriate addition and subtraction in dosage. The early postoperative period features qi stagnation and blood stasis, and less significantly, liver and kidney difficiency, when the medication shall be focused on activating blood circulation to dissolve blood stasis, so as to relieve swelling and pain and promote circulation of qi. In the middle and late period, with liver and kidney deficiency as the main symptom and qi stagnation and blood stasis less significant, the treatment should be focused on tonifying the kidney and liver, combined with the activation of blood circulation and promotion of qi.
The clinical study and animal experiments show that the treatment can effectively control the increase of the TNF-a, MMP-3 and NO levels after the articular fracture fixation operation and that using invigorating kidney and promoting blood flow treament of syndrome differentiation can effectively prevent and control the pathological change process of Post-traumatic Osteoarthritis after the articular fracture operations.
According to the research results of the clinical observation, the treatment group using invigorating kidney and promoting blood flow treament have the effects on the control of body pain and the recovery of physical functions similar to that of the commonly used Celebrex and better than that of the blank group. At the same time, invigorating kidney and promoting blood flow treament have an evident curative effect on TCM symptoms. This shows that invigorating kidney and promoting blood flow treament can prevent and control the pathological change process of Post-traumatic Osteoarthritis after the articular fracture operations, ease pain, promote function recovery and improve the curative effects on clinical treatment and rehabilitation.
In a word, the research results show that using invigorating kidney and promoting blood flow treament with syndrome differentiation can prevent and control the pathological change process of cartilage cataplasia after the articular fracture operations, can promote the healing process of the joint function of the patients after the articular fracture operations for a better curative effect and can have overall conditioning and rehabilitation effects on the patients after the articular fracture operations for a better quality of life.
Therefore, according to the research conclusion, invigorating kidney and promoting blood flow treament can control the generation and development process of cartilage cataplasia after the articular fracture operations, promote the healing process of the joint function of the patients after the articular fracture operations and have overall conditioning and rehabilitation effects on the patients for a better quality of life, so as to effectively prevent and control the cartilage cataplasia after the articular fracture operations.
近年来,随着高能量损伤致关节软骨损伤的机率增大,创伤性关节炎的发病率呈现逐年增加的趋势。因其临床主要表现为受累关节的疼痛、不同程度的关节活动障碍,严重者有畸形改变,甚至致残,后果严峻：因此一直是临床治疗关注的焦点和难点。
研究目的
通过临床研究和动物实验,探讨运用补肾活血方药辨证施治用药,能否有效影响关节骨折术后的关节软骨退变相关因子；能否从整体上对关节骨折术后患者产生调理,促进关节骨折术后患者关节功能的康复过程,提高疗效。
研究内容和方法
采用临床研究及动物实验研究。
临床研究
临床资料及方法：选取临床收治涉膝关节关节面的高能量损伤骨折并进行内固定术后患者约60人,设补肾活血组、西乐葆组和空白组。另从健康志愿者中选取20人作为正常对照组。补肾活血组予以活血补肾方汤剂口服。
临床研究一：于术后1周、3周及8周,进行血清和关节液TNF-a、MMP-3和NO浓度检测。
临床研究二：术后3周和8周,通过对相关症状、体征及中医证候进行综合计分来进行疗效评价。
动物实验研究
选择成年雄性SD大鼠40只采用完全随机设计,分成正常组,补肾活血组,西乐葆组和空白组,每组10只。术后3天,7天及21天进行血清和关节液TNF-a、MMP-3和NO浓度检测。
研究结果
通过临床研究,我们发现,各组1周、3周和8周TNF-a和NO水平有逐渐升高趋势,两两比较均有显著性差异。而各组3周到8周的血清及关节液TNF-a水平间存在相关关系。说明这期间MMP-3的升高与TNF-a水平增高相关。同时,在3周和8周的对比中,空白组关节液和血清TNF-a、MMP-3和NO的水平均显著高于补肾活血组。说明应用补肾活血法的补肾活血组对这期间的TNF-a、MMP-3和NO的水平增长能有效抑制。
临床疗效评价：3周时功能计分和总计分,三组患者的计分均无显著性差异(P>0.05),说明3周时三组患者病情具有可比性。8周时三组患者所有项目计分均较3周时改善(P<0.05)。疼痛计分,西乐葆组均显著高于其他两组(P<0.05),而补肾活血组在8周时优于空白组(P<0.05)。8周时三组患者的总计分和功能计分比较,补肾活血组和西乐葆组差异均无显著性意义(P>0.05)；但优于空白组(P<0.05)。中医证候计分比较,补肾活血组均显著高于其他两组(P<0.05)。疾病疗效比较补肾活血组与西乐葆组的疾病疗效相仿(P>0.05),而空白组较两组低(P<0.05)。补肾活血组的中医证候疗效高于西乐葆组和空白组(P<0.05)。
动物实验研究显示,补肾活血组在抑制血清TNF-a、MMP-3及NO等水平升高方面明显优于空白对照组。各组TNF-a、MMP-3及NO水平变化进程和临床实验研究结果相近。
研究结论
在本研究中,辨证认为关节骨折术后的关节软骨退变,多以肝肾不足为本,气滞血瘀为标。故针对此病机证候,治法应以补肾活血为主。同时,根据术后具体病机证候变化,辨证用药,适当加减。术后早期,气滞血瘀证为主,肝肾不足为次,因此治疗以加强活血祛瘀之方药,以消肿止痛,行气和营。中后期,则以肝肾不足为主,气滞血瘀之证为次。故治疗以补肾养肝为重而兼以活血行气之功。
通过临床和动物实验室检验结果证实,补肾活血组对关节骨折固定术后的TNF-a、MMP-3和NO水平增长能有效抑制；证明运用补肾活血方药辨证施治用药,能有效防治关节骨折术后的关节软骨退变进程。
而根据临床观察研究结果,应用补肾活血法的补肾活血组,在关节骨折创伤术后的疼痛控制,功能恢复方面和临床常用药物西乐葆的功效相近,而优于空白对照组。同时,补肾活血法在治疗中医证候方面疗效明显。因此可证实,补肾活血法能有效防治关节骨折创伤术后关节软骨退变进展,缓解疼痛和促进功能恢复,提高临床治疗和康复的疗效。
综上所述,根据研究实验结果,可以证实：运用补肾活血方药辨证施治用药,能有效影响关节骨折术后的团结软骨退变相关因子。补肾活血法能从整体上对关节骨折术后患者产生调理,促进关节骨折术后患者关节功能的康复过程,提高疗效。
由此,研究结论认为补肾活血法在对于抑制关节骨折后关节软骨退变的进程,并促进关节骨折术后患者关节功能的康复方面,产生积极和有利的影响。
Post-traumatic Osteoarthritis is a kind of osteoarthritis resulting from joint trauma and a kind of joint dysfunction resulting from cartilage denaturalization and destruction in movable joints due to continuous physical or mechanical damages and from the subsequent changes in articular cartilage, subchondral bone, synovium, joint capsule and surrounding muscles and ligaments.
In recent years, with the increase of the probability of high energy traumas caused by articular cartilage injury, the incidence rate of the Post-traumatic Osteoarthritis has been rising year by year. Its main clinical features include the pain in involved joints, joint movement disorder in different degrees and even malformation or disability, which has made it a focus and difficulty in clinical treatment.
Objective
Through clinical studies and animal experiments, discuss whether using invigorating kidney and promoting blood flow treament of syndrome differentiation can effectively prevent and control the pathological change process of cartilage cataplasia after the articular fracture operations, can promote the healing process of the joint function of the patients after the articular fracture operations for a better curative effect and can have overall conditioning and rehabilitation effects on the patients after the articular fracture operations for a better quality of life.
Methods
Clinical Study and Animal Experiments are adopted.
Clinical Study
Clinical data and methods:Choose about 60 patients suffering from high-energy post-traumatic fracture involved with knee and ankle joints' articular surfaces, who have go through the internal fixation operations, to set up a treatment group, a Celebrex group and a blank group. And choose 20 non-fracture patients to set up a normal control group. The treatment group will take the oral medication of invigorating kidney and promoting blood flow treament.
Clinical Study 1:In the 1st,3rd and 8th weeks after operation, measure the TNF-a, MMP-3 and NO concentrations in terms of serum and synovial fluid.
Clinical Study 2:Three weeks and eight weeks after operation, evaluate the curative effect by means of overall scoring on the related symptoms, physical signs and TCM symptoms.
Animal Experiments
Choose 40 adult male SD rats and divide them into a normal group, a treatment group, a Celebrex group and a blank group by means of completely random design, with 10 in each group. On the 3rd,7th and 21st days after operation, measure the TNF-a, MMP-3 and NO concentrations in terms of serum and synovial fluid.
Results
Through the clinical study, we have found out that there is a gradual increase in the TNF-a and NO concentrations in each group on the 1st,3rd and 8th weeks after operation, with significant deviation between each two groups. However, the TNF-a levels of the serum and of the synovial fluid in each group are correlated in the 3-8 weeks. This shows that the increase of MMP-3 is related to that of the TNF-a level during this period. In the meantime, when comparing the data of the 3rd week with that of the 8th week, the TNF-a, MMP-3 and NO levels of the blank group in terms of serum and synovial fluid are all much higher than that of the treatment group. This shows that the treatment group adopting invigorating kidney and promoting blood flow treament can effectively control the increase of the TNF-a, MMP-3 and NO levels during this period.
Clinical Effect Evaluation:With reference to the function scoring and total scoring, there are little difference among the scorings of all the three groups (P> 0.05), which shows that the three groups'illness is comparable in the 3rd week. All the scorings of the three groups in the 8th week are better than that in the 3rd week (P<0.05). In terms of pain scoring, the Celebrex group are much better than the other two groups (P<0.05), while the treatment group exceeds the blank group in the 8th week (P<0.05). Judging from the comparison between the total scorings and function scorings of the three groups in the 8th week, the difference in the treatment group and the Celebrex group are of no significance (P>0.05); but they are better than the blank group (P<0.05). In terms of TCM symptom scoring, the treatment group's scores are all higher than that of the other two groups (P<0.05). As to the curative effects, the treatment group is similar to the Celebrex group (P>0.05), both better than the blank group (P<0.05). The treatment group is better than the Celebrex group and the blank group in terms of the curative effects on TCM symptoms (P<0.05).
The animal experiments show that the treatment group is much better than the blank group in terms of the control of the increase of the TNF-a, MMP-3 and NO levels of serum. The changing process of each group's TNF-a, MMP-3 and NO levels is close to the results of the clinical experiments. Conclusion
In this research, syndrome differentiation shows that the Post-traumatic Osteoarthritis occurring after the articular fracture operation is generally based on the liver and kidney deficiency with qi stagnation and blood stasis as the standard. Therefore, invigorating kidney and promoting blood flow treament is the prevailing therapy. Meanwhile, according to the changes in specific symptoms after operation, adopt syndrome differentiation with appropriate addition and subtraction in dosage. The early postoperative period features qi stagnation and blood stasis, and less significantly, liver and kidney difficiency, when the medication shall be focused on activating blood circulation to dissolve blood stasis, so as to relieve swelling and pain and promote circulation of qi. In the middle and late period, with liver and kidney deficiency as the main symptom and qi stagnation and blood stasis less significant, the treatment should be focused on tonifying the kidney and liver, combined with the activation of blood circulation and promotion of qi.
The clinical study and animal experiments show that the treatment can effectively control the increase of the TNF-a, MMP-3 and NO levels after the articular fracture fixation operation and that using invigorating kidney and promoting blood flow treament of syndrome differentiation can effectively prevent and control the pathological change process of Post-traumatic Osteoarthritis after the articular fracture operations.
According to the research results of the clinical observation, the treatment group using invigorating kidney and promoting blood flow treament have the effects on the control of body pain and the recovery of physical functions similar to that of the commonly used Celebrex and better than that of the blank group. At the same time, invigorating kidney and promoting blood flow treament have an evident curative effect on TCM symptoms. This shows that invigorating kidney and promoting blood flow treament can prevent and control the pathological change process of Post-traumatic Osteoarthritis after the articular fracture operations, ease pain, promote function recovery and improve the curative effects on clinical treatment and rehabilitation.
In a word, the research results show that using invigorating kidney and promoting blood flow treament with syndrome differentiation can prevent and control the pathological change process of cartilage cataplasia after the articular fracture operations, can promote the healing process of the joint function of the patients after the articular fracture operations for a better curative effect and can have overall conditioning and rehabilitation effects on the patients after the articular fracture operations for a better quality of life.
Therefore, according to the research conclusion, invigorating kidney and promoting blood flow treament can control the generation and development process of cartilage cataplasia after the articular fracture operations, promote the healing process of the joint function of the patients after the articular fracture operations and have overall conditioning and rehabilitation effects on the patients for a better quality of life, so as to effectively prevent and control the cartilage cataplasia after the articular fracture operations.
引文
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[6]Kafka V. Suraface fissures in articular cartilage:new concepts, Hypotheses and modeling. Clin Biomech(bristol, Avon),2002,7 (1):73-74.
[7]朱宝玉,陈琼,王万春,等.创伤后关节软骨中MMP-3的表达及意义[J].实用骨科杂志,2006,12(1)：35-37.
[8]Trumble T, Verheyden J. Remodeling of a articular defects in ananimal model. Clin Orthop,2004,423:59.
[9]Matyas JR, Atley L, Inescu M, etal. Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis. Arthritis Rheum, 2003,50 (2):543.
[10]Martin JA, Brown TD, Heiner AD, etal. Chondrocyte senescence, joint loading and osteoarthritis. Clin Orthop,2004,427(supp):96.
[11]Loening AM, James IE, Levenston ME, et al. Injurious mechanicalcompression of bovine articular cartilage induces chondrocyte apoptosis[J]. Arch Biochem Biophys,2000,381:205～212.
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[13]Haut RC, lde TM,/camp CE. Mechanical responses of the rabbit patello-femoral joint to blunt impact[J]. J Biomech,1995,117:402～408.
[14]Newberry WN, Zukosky DK, Haut RC. Subfraeture insult to a knee joint causes alterations in the bone and in the functional stiffness of Overlying cartilage [J]. J Orthop Res,1997,15:450～455.
[15]Newberty WN, Garcia jj, Mackenzie CD, etal. Analysis of acutemechanical insalt in an animalmodel of post-traumatic osteoar-throsis. Bonnech Eng, 1998,120(6):704.
[16]Lin PM, Chen CT, Torzilli PA. Increased stromelysin-1(MMP-3), proteoglycan degradation (3B3 and 7D4)and collagen damage in cyclically load-injured articular cartilage. Osteoarthritis Cartilage,2004,12(6):485.
[17]Buckwalter JA, Rosenberg LC, Coutts R, et al. Articular Cartilage:Injury and Repair[M]. In Woo SL, Buckwalter JA(eds). Injury and Repair of the Musculockeletal Soft Tissues. Park Ridge, IL, AmericanAcademy of Orthopaedic Surgeons,1988.465～482.
[18]Martin JA, Buckwalter JA. The role of chondrocyte-matrix interactionsin maintaining and repairing articular carthage[J]. Biorheology2000,37:129～ 140.
[19]Buckwalter JA, Einhom TA, Bolander ME, et al. Healing of Musculoskeletal Tissues[M]. In Rockwood CA, Green D(eds). Fractures. Philadelphia, Lippincott 1996.261～304.
[20]Kim HT, Lo MY, Pillarisetty R. Chondrocyte apoptosis following intra articular fracture in humans. Osteoarthritis Cartilage,2002,10(9):747.
[21]Hashimoto S, Takahashis K, Amiel D, etal. Chondrocyte apoptosis and nitric oxide produtcion during experimentally induced osteoarthritis. Arthritis Rhenum,1998, (41):1266.
[22]Martin JA, Brown T, Heiner A, etal. Post-traumatic osteoar-thritis, the role of accelerated chondrocyte senescence. Biorheology,2004,41(3-4):479.
[23]夏睿,董启榕.兔创伤性骨关节炎软骨细胞中基质金属蛋白酶13表达增加[J].基础医学与临床,2007,27(2)：202-205.
[24]DiMicco MA, Patwari P, Siparsky PN, etal. Mechanisma and kinetics of glycosaminogly can release following in vitro cartilage injury. Arthritis Rheum,2004,50(3):840-842.
[25]Lee JH, Gitzgerald JB, Dimicco MA, etal. Mecanical injury of cartilage explants causes specific time-dependent chargesin chondrocyte gene expression. Arthritis Theum,2005,52(8):2386-2388.
[26]Ie Graverand MP, Eggerer J, Vignon E, etal. Assessment of specific mRNA levels in cartilage regions in a lapine model of osteoarthritis. J Orthop Res, 2002,20(3):535-536.
[27]Sasaki K, Hattori T, Fujisawa T, etal. Nitric oxide mediatesinterleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes. J Biochem(Tokyo), 1998,123(3):431-433.
[28]Anderson DG, Izzo MW, Hall DJ, etal. Comparative gene expression profiling of normal and degenerative discs:analysis of a rabbit annular laceration model. Spine,2002,27(12):1291-1294.
[29]Baeuerle PA. Pro-inflammatory signaling:last pieces in the NF-kb puzzle, Curr Biol,1998,8:19-21.
[30]Karin M, Delhase M. JNK or IKK, AP-1 or NF-kb, which are the targets for MEK kinase-laction? Proc natl Acad Sci USA,1998,95:9067-9069.
[31]Barnes PJ. Molecules in focus:Nuclear factor-Kappa B. Int JB Biochem Cell Boil,1997,29(6):867-869.
[32]陈连旭,于长隆,王海军,等.核因子-κBP65蛋白在大鼠创伤性骨关节炎中的表达[J].中国运动医学杂志,2007,26(4)：427-429.
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