注射性臀肌挛缩症发病机理与临床研究
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摘要
目的研究不同方法建立注射性臀肌挛缩症动物模型的可行性及b-FGF、MMP1和TIMP1、MMP2和TIMP2在臀肌挛缩症发病中的意义；制订臀肌挛缩症评分量表,并对其效能进行统计学检验；对臀肌挛缩症进行临床分型,评价分型的可靠性,探讨关节镜下微创治疗臀肌挛缩症的疗效。
方法1、采用不同注射药物建立注射性臀肌挛缩症的动物模型,对兔臀肌注射后改变进行病理观察,分析不同方法建立动物模型的特点；采用免疫组织化学的方法,分析b-FGF、MMP1和TIMP1、MMP2和TIMP2在臀肌挛缩症发病过程的表达和意义。2、制订臀肌挛缩症评分量表,评估其内在一致性、信度、效度和反应性。3、对臀肌挛缩症进行临床分型,分析其在观察者之间与观察者自身间的一致性；采用制订的臀肌挛缩症评分量表,对关节镜下微创治疗臀肌挛缩症的疗效进行评估。
结果1、青霉素+苯甲醇和青霉素+无菌注射用水在兔臀肌长期注射后均能形成臀肌挛缩症动物模型,青霉素+苯甲醇组建立的动物模型其胶原等细胞外基质分泌更多,纤维化程度更高。免疫组织化学显示b-FGF在病变过程中可见不同程度的阳性表达,随时间延长,其阳性表达增多；TIMP1、MMP2知TIMP2在发病过程中均出现阳性表达,随着病情进展,MMPs/TIMPs比值发生改变。2、评分量表的内容效度良好,结构效度分析显示各因素之间Spearman秩相关系数多在0.55-0.75之间,呈中等程度相关,各因素与量表总分之间Spearman秩相关系数多在0.70-0.90之间,呈高度相关；内在一致性检验Cronbach's a系数在0.8310-0.9087之间；重测信度示观察者之间ICC为0.90(0.84-0.93),观察者自身ICC为0.92(0.88-0.95)；量表反应性评估示ES=3.64,SRM=3.97。3、臀肌挛缩症分型的研究显示医生分型与手术分型的一致性很好,Kappa=0.859-0.975;医生之间分型的一致性检验良好,Kappa=0.726-0.867;医生重复分型的一致性检验良好,Kappa=0.749-0.838。91例患者术前平均得分55.25分,术后平均得分93.50分,配对t检验示两者之间存在显著的统计学差异。
结论1、青霉素+苯甲醇和青霉素+无菌注射用水连续注射均可造成臀肌挛缩症动物模型,以青霉素+苯甲醇组建立的动物模型更明显；b-FGF、TIMP1和TIMP2在臀肌挛缩症发病过程中起到重要作用,为我们早期预防与治疗臀肌挛缩症提供了新的研究方向。2、臀肌挛缩症评分量表具有良好的内在一致性、重测信度、结构效度、内容效度和反应性,是评价臀肌挛缩症患者功能与疗效的标准。3、臀肌挛缩症分型有助于临床治疗；关节镜下治疗臀肌挛缩症较开放手术具有微创、安全和功能恢复快等优势,具有重要的临床应用价值。
Objective: To study the feasibility of developing injectable gluteal musclecontracture (GMC) animal model using different methods, and to investigate the role ofb-FGF, MMP1and TIMP1, MMP2and TIMP2in the pathogenesis of injectable GMC. Todevelop the clinical rating scale of GMC and to evaluate it’s psychometric propertiesincluding reliability, agreement, validity and responsiveness. Develop a new clinicalclassification of GMC, and to evaluate its reliability. Assess the efficacy of arthroscopicminimally invasive treatment of GMC using the clinical rating scale which developedprevious.
Method:1. We used different injectable drugs to develop injectable GMC animalmodel in rabbits, and analyzed the characteristics of different animal models through thepathological change of the gluteal muscle in rabbits after injection. We analyzedthe expression and significance of the b-FGF, MMP1and TIMP1, MMP2andTIMP2in the GMC progression using immunohistochemical method in the most reliableGMC animal model.2. We developed the GMC clinical rating scale relying on the reviewof litetature, the clinical practice and the interview of both the patients and the doctors, andevaluated the internal consistency, validity, interrater and intrarater agreement, andresponsiveness of the rating scale in67patients and two orthopedic physicians.3. Wedeveloped a new clinical classification of GMC through clinical practice and intraoperativefindings, and assessed its consistency using interobserver and intraobserverreliability analysis among91patients by three doctors, and we evaluated the efficacy ofarthroscopic minimally invasive treatment of GMC using the rating scale that developedprevious among the91patients.
Results:1. Long-term and frequent injection of penicillin+phemethylol or penicillin+Sterile Water for Iinjection (SWFI) in gluteus muscle of rabbits could both develop GMC animal models successfully, the injeciton of penicillin+phemethylol could lead to more secretion and formation of collagen and other extracellularmatrix than injection of penicillin+SWFI in gluteal muscle of the animal model.Immunohistochemistry showed that the positive expression of b-FGF was found in thedamaged muscle and increased with the GMC progression, the positive expressionof TIMP1, MMP2and TIMP2was also found in the GMC progression, and the ratio ofMMPs/TIMPs had changed with the GMC progression.2. The GMC rating scale wedeveloped was found to have good content validity, high contruct validity (Spearman rankcorrelation coefficient was0.55-0.75among the sub-items, and0.70-0.90between thesub-items and the total project): high internal consistency (Cronbach's α=0.8310-0.9087):excellent interrater reliability (ICC=0.90): intrarater reliability (ICC=0.92) andresponsivenee (ES=3.64, SRM=3.97).3. The agreement of the new clinicalclassification of GMC was good; the Kappa value was0.859to0.975between the doctorsand the standard classification,0.726to0.867between different doctoes and0.749to0.838between different times examined by the same doctor. The GMC rating score of thepatients suffered GMC was55.25preoperatively and93.50postoperatively, all patientswere satisfied with the functional recovery from their disease.
Conclusion:1. Injection of penicillin+phemethylol or penicillin+SWFI could bothdevelop GMC animal models successfully; the GMC animal model developed by injectionof penicillin+phemethylol is more fitable for pathogenesis research of GMC. b-FGF,TIMP1and TIMP2might play an important role in the progession of GMC, and it couldprovide some new research directions for the prevention and early treatment of GMC.2.The GMC rating scale has good internal consistency, test-retest reliability, construct andcontent validity, and responsiveness, it is an ideal psychological measurement tools in theassessment of the functional status of GMC patients.3. The new classification of GMCwill be conducive to clinical treatment. Arthroscopic treatment of GMC has advantages ofminimally invasive, safe and quick functional recovery compared with open surgery.
方法1、采用不同注射药物建立注射性臀肌挛缩症的动物模型,对兔臀肌注射后改变进行病理观察,分析不同方法建立动物模型的特点；采用免疫组织化学的方法,分析b-FGF、MMP1和TIMP1、MMP2和TIMP2在臀肌挛缩症发病过程的表达和意义。2、制订臀肌挛缩症评分量表,评估其内在一致性、信度、效度和反应性。3、对臀肌挛缩症进行临床分型,分析其在观察者之间与观察者自身间的一致性；采用制订的臀肌挛缩症评分量表,对关节镜下微创治疗臀肌挛缩症的疗效进行评估。
结果1、青霉素+苯甲醇和青霉素+无菌注射用水在兔臀肌长期注射后均能形成臀肌挛缩症动物模型,青霉素+苯甲醇组建立的动物模型其胶原等细胞外基质分泌更多,纤维化程度更高。免疫组织化学显示b-FGF在病变过程中可见不同程度的阳性表达,随时间延长,其阳性表达增多；TIMP1、MMP2知TIMP2在发病过程中均出现阳性表达,随着病情进展,MMPs/TIMPs比值发生改变。2、评分量表的内容效度良好,结构效度分析显示各因素之间Spearman秩相关系数多在0.55-0.75之间,呈中等程度相关,各因素与量表总分之间Spearman秩相关系数多在0.70-0.90之间,呈高度相关；内在一致性检验Cronbach's a系数在0.8310-0.9087之间；重测信度示观察者之间ICC为0.90(0.84-0.93),观察者自身ICC为0.92(0.88-0.95)；量表反应性评估示ES=3.64,SRM=3.97。3、臀肌挛缩症分型的研究显示医生分型与手术分型的一致性很好,Kappa=0.859-0.975;医生之间分型的一致性检验良好,Kappa=0.726-0.867;医生重复分型的一致性检验良好,Kappa=0.749-0.838。91例患者术前平均得分55.25分,术后平均得分93.50分,配对t检验示两者之间存在显著的统计学差异。
结论1、青霉素+苯甲醇和青霉素+无菌注射用水连续注射均可造成臀肌挛缩症动物模型,以青霉素+苯甲醇组建立的动物模型更明显；b-FGF、TIMP1和TIMP2在臀肌挛缩症发病过程中起到重要作用,为我们早期预防与治疗臀肌挛缩症提供了新的研究方向。2、臀肌挛缩症评分量表具有良好的内在一致性、重测信度、结构效度、内容效度和反应性,是评价臀肌挛缩症患者功能与疗效的标准。3、臀肌挛缩症分型有助于临床治疗；关节镜下治疗臀肌挛缩症较开放手术具有微创、安全和功能恢复快等优势,具有重要的临床应用价值。
Objective: To study the feasibility of developing injectable gluteal musclecontracture (GMC) animal model using different methods, and to investigate the role ofb-FGF, MMP1and TIMP1, MMP2and TIMP2in the pathogenesis of injectable GMC. Todevelop the clinical rating scale of GMC and to evaluate it’s psychometric propertiesincluding reliability, agreement, validity and responsiveness. Develop a new clinicalclassification of GMC, and to evaluate its reliability. Assess the efficacy of arthroscopicminimally invasive treatment of GMC using the clinical rating scale which developedprevious.
Method:1. We used different injectable drugs to develop injectable GMC animalmodel in rabbits, and analyzed the characteristics of different animal models through thepathological change of the gluteal muscle in rabbits after injection. We analyzedthe expression and significance of the b-FGF, MMP1and TIMP1, MMP2andTIMP2in the GMC progression using immunohistochemical method in the most reliableGMC animal model.2. We developed the GMC clinical rating scale relying on the reviewof litetature, the clinical practice and the interview of both the patients and the doctors, andevaluated the internal consistency, validity, interrater and intrarater agreement, andresponsiveness of the rating scale in67patients and two orthopedic physicians.3. Wedeveloped a new clinical classification of GMC through clinical practice and intraoperativefindings, and assessed its consistency using interobserver and intraobserverreliability analysis among91patients by three doctors, and we evaluated the efficacy ofarthroscopic minimally invasive treatment of GMC using the rating scale that developedprevious among the91patients.
Results:1. Long-term and frequent injection of penicillin+phemethylol or penicillin+Sterile Water for Iinjection (SWFI) in gluteus muscle of rabbits could both develop GMC animal models successfully, the injeciton of penicillin+phemethylol could lead to more secretion and formation of collagen and other extracellularmatrix than injection of penicillin+SWFI in gluteal muscle of the animal model.Immunohistochemistry showed that the positive expression of b-FGF was found in thedamaged muscle and increased with the GMC progression, the positive expressionof TIMP1, MMP2and TIMP2was also found in the GMC progression, and the ratio ofMMPs/TIMPs had changed with the GMC progression.2. The GMC rating scale wedeveloped was found to have good content validity, high contruct validity (Spearman rankcorrelation coefficient was0.55-0.75among the sub-items, and0.70-0.90between thesub-items and the total project): high internal consistency (Cronbach's α=0.8310-0.9087):excellent interrater reliability (ICC=0.90): intrarater reliability (ICC=0.92) andresponsivenee (ES=3.64, SRM=3.97).3. The agreement of the new clinicalclassification of GMC was good; the Kappa value was0.859to0.975between the doctorsand the standard classification,0.726to0.867between different doctoes and0.749to0.838between different times examined by the same doctor. The GMC rating score of thepatients suffered GMC was55.25preoperatively and93.50postoperatively, all patientswere satisfied with the functional recovery from their disease.
Conclusion:1. Injection of penicillin+phemethylol or penicillin+SWFI could bothdevelop GMC animal models successfully; the GMC animal model developed by injectionof penicillin+phemethylol is more fitable for pathogenesis research of GMC. b-FGF,TIMP1and TIMP2might play an important role in the progession of GMC, and it couldprovide some new research directions for the prevention and early treatment of GMC.2.The GMC rating scale has good internal consistency, test-retest reliability, construct andcontent validity, and responsiveness, it is an ideal psychological measurement tools in theassessment of the functional status of GMC patients.3. The new classification of GMCwill be conducive to clinical treatment. Arthroscopic treatment of GMC has advantages ofminimally invasive, safe and quick functional recovery compared with open surgery.
引文
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