【作者】 杨久山；

【导师】 徐展望；

【作者基本信息】 山东中医药大学 ， 中医骨伤科学， 2013， 博士

【摘要】 目的：1．研究和探讨独活寄生汤治疗骨性关节炎的作用和作用机理，同时观察独活寄生汤结合关节镜下关节清理术对骨性关节炎的协同治疗作用。2．通过膝骨性关节炎患者治疗前后的三维步态分析，探讨三维动作捕捉系统在KOA功能康复中的应用。方法1.观察独活寄生汤对骨性关节炎兔关节液中IL-1β、IL-6、TNF-α以及MMP-3的影响34只新西兰兔，随机分为3组，模型组12只，应用石膏固定法造模，造模42天后每日10ml0.9%生理盐水灌服，连服6周；治疗组12只，造模42天后每日10ml独活寄生汤药液灌服，连服6周；空白组10只，不造模，不喂药。取其膝关节液，应用酶联免疫法检测IL-1β、IL-6、TNF-α以及MMP-3的含量，进行三组间各炎性因子和MMP-3水平的比较。2.观察独活寄生汤对骨性关节炎患者关节液中IL-1β、IL-6、TNF-α以及MMP-3的影响筛选54位膝骨关节炎患者，服用独活寄生汤加减治疗，治疗期间杜绝其他药物和治疗，6周后抽取患者的膝关节液，应用酶联免疫法检测IL-1β、IL-6、TNF-α以及MMP-3的含量，比较治疗前后的细胞因子和MMP-3水平变化。3.独活寄生汤结合关节清理术对膝骨性关节炎的作用选择符合条件的36位膝骨性关节炎患者，随机分为两组，一组仅行关节清理术，另一组关节清理术后服用独活寄生汤加减，随访6个月以上，比较手术前后的Lysholm膝关节评分和疼痛单项评分，以及两组患者JOA主观评定分级结果评价。4.膝骨性关节炎患者的三维步态分析将24名膝骨性关节炎患者和6名健康志愿者作为受试对象，分为中药组、手术组、中药+手术组、空白组和正常组5组，每组6人，应用VICON三维运动捕捉系统进行步态采集和分析，计算其平均步幅、步频、步速等时间-空间参数，以及髋、膝、踝三关节在步态周期中的最大屈曲角度，各组间参数均数进行两两比较。结果造模42天、灌胃6周后检测各组实验兔的关节液中IL-1β、IL-6、TNF-α以及MMP-3含量分别是：模型组IL-1β259.71±19.956pg/ml,IL-6273.5±47.528pg/ml,TNF-α7.163±0.758ng/ml,MMP-316.824±1.674ng/ml;治疗组IL-1β145.74±18.755pg/ml,IL-6128.76±15.668pg/ml,TNF-α3.263±0.234ng/ml,MMP-39.418±0.424ng/ml;空白组IL-1β25.52±6.614pg/ml,IL-619.32±3.773pg/ml,TNF-α1.249±0.201ng/ml,MMP-31.04±0.052ng/ml统计学检验各检测因子的含量组间比较均为P<0.05,存在显著性差异。54例骨性关节炎患者服用独活寄生汤治疗前后关节液中的含量分别是IL-1β治疗前815.551±95.595pg/ml,治疗后557.264±5.253pg/ml； IL-6治疗前1401.783±185.057pg/ml,治疗后995.131±126.482pg/ml;TNF-α治疗前112.355±14.67ng/ml,治疗后74.883±8.389ng/ml;MMP-3治疗前10.919±1.173ng/ml,治疗后8.707±1.128ng/ml。治疗前后比较P<0.05，有显著性差异。36位关节炎患者中手术组Lysholm膝关节评分由术前的52.6±8.8分提高到术后的85.8±6.2分，疼痛单项评分由术前的6.5±3.0提高到术后的18.8±4.9分；中药+手术组评分由术前的50.2±7.6分提高到术后的87.2±6.5分，疼痛单项评分由术前的6.5±3.0提高到术后的20.5±4.9分；两组患者主观评定结果：手术组优2例，良11例，可4例，差1例，优良率72.2%；手术组手术组优3例，良12例，可3例，差0例，优良率83.3%。统计学分析Lysholm评分和疼痛单项评分在治疗前后均有统计学意义，提示具有治疗作用，但两组间比较无统计学意义，说明两种方法疗效按Lysholm评分标准和疼痛单项评分没有差别。患者主观评定结果具有显著性差别。5组受试者的三维运动分析结果：中药组、手术组、中药+手术组、空白组和正常组步幅（m）分别为0.536±0.061，0.615±0.0670.681±0.0790.503±0.0470.754±0.080，步频（1/s）分别为1.065±0.1311.164±0.1391.289±0.1620.951±0.1011.581±0.118，步速（m/s）分别为0.571±0.0710.881±0.0790.966±0.0860.478±0.0431.192±0.123，髋关节屈曲最大角度（0）8.440±0.9778.588±1.0038.963±1.1118.711±0.95010.293±1.523，膝关节最大屈曲角度（0）54.343±5.46957.210±4.80858.627±6.10352.266±5.44059.529±6.740，踝关节跖屈最大角度（0）21.012±1.96123.188±2.57124.577±2.76519.843±2.16422.771±2.119。5组比较，步幅、步速各组间差异明显，步频无明显差别，各关节最大屈曲角度无差别。结论1.独活寄生汤可以抑制膝关节液中IL-1β、IL-6、TNF-α及MMP-3的表达，从而对KOA具有治疗作用。2.关节清理术能够提高患者Lysholm膝关节评分，并能提高步态周期中的步幅和步速，说明关节清理术对KOA具有治疗作用，能够缓解关节疼痛，改善关节功能。3.独活寄生汤结合关节清理术治疗KOA，可以起到协同治疗作用。4.三维动作捕捉系统能够准确捕捉并分析步态特征，可以作为评估下肢功能康复的有效方法。更多还原

【Abstract】 Objective：1.To research the effect and mechanism of duhuojisheng decoction on KOA,anddiscuss the synergistic effect of duhuojisheng decoction and arthroscopic debridment.2.By analysing the3D gait of prior and post treatment,discuss the application of3Dmotion capture system for functional rehabilitation of KOA.Methods：1.Influence of duhuojisheng decoction on synovial fluid from knee joints of rabbitswith osteoarthritis,by detecting the level of IL-1β、IL-6、TNF-α and MMP-3.34New Zealand rabbits were divided randomly into3groups,model group(12rabbits,immobilizing with gypsum for42days,then given saline water10ml per day,lasting6weeks),treatment group(12rabbits,the same way fixed after42days,then gave lavage dietof duhuojisheng decoction10ml per day,lasting6weeks), control group (10rabbits,givennothing),detect IL-1β、IL-6、TNF-αand MMP-3in synovial fluid using enzyme linkedimmunosorbent assay(ELISA) way,and then compared the level of each group.2.Influence of duhuojisheng decoction on synovial fluid of knee joints in patients withosteoarthritis.54KOA patients were treated with duhuojisheng decoction for6weeks,then collectthe samples of synovial fluid and detectthe level of IL-1β、IL-6、TNF-αand MMP-3byenzyme linked immunosorbent assay(ELISA),and compared the prior and post treatmentlevel of each group.3.The effects of duhuojisheng decoction and arthroscopic debridment on kneeosteoarthritis36patients with KOA were randomly divided into two groups, one proup were treated with arthroscopic debridment and another group duhuojisheng decoction combining witharthroscopic debridment,and they were followed up for an average period of6months,Lysholm functional scale of the knee and JOA scores were collected including prior andpost treatment.4.3D gait analysis of the patients with knee osteoarthritis(KOA)24patients with KOA were randomly divided into four groups,traditional Chinesemedicine group,operation group,traditional Chinese medicine and operation group, and theblank control group,every group composed of6patients,another6healthy volunteers madeup of the normal group. VICON3D motion capture system were applied to measure andcalculate kinematic parameters such as stride time、 cadence、 velocity and themaximum-flexion of the hip、knee and ankle joints,then analysis the difference of eachgroup.Results：After given duhuojisheng decoction for6weeks, the data of synovial fluid in modelgroup were IL-1β(259.71±19.956pg/ml)、 IL-6(273.5±47.528pg/ml)、 TNF-α (7.163±0.758ng/ml), MMP-3(16.824±1.674ng/ml)；treatment group IL-1β145.74±18.755pg/ml,IL-6128.76±15.668pg/ml,TNF-α3.263±0.234ng/ml,MMP-39.418±0.424ng/ml;blankgroup IL-1β25.52±6.614pg/ml,IL-619.32±3.773pg/ml,TNF-α1.249±0.201ng/ml,MMP-31.04±0.052ng/ml.P<0.05indicate that there is statistic difference among3groups.The data of synovial fluid in54patients with KOA after taking duhuojishengdecoction presented a intended result:IL-1β(prior treatment815.551±95.595pg/ml,posttreatment557.264±5.253pg/ml)； IL-6(prior treatment1401.783±185.057pg/ml,posttreatment995.131±126.482pg/ml)； TNF-α(prior treatment112.355±14.671ng/ml,posttreatment74.883±8.389ng/ml)；MMP-3(prior treatment10.919±1.173ng/ml，post treatment8.707±1.128ng/ml），P<0.01indicate that there is statistic difference,too.In36patients with KOA,the Lysholm functional score of the knee raised from52.6±8.8to85.8±6.2,the singe pain score raised from6.5±3.0to18.8±4.9；in theduhuojisheng decoction and arthroscopic debridment group,the Lysholm functional scoreof the knee raised from50.2±7.6to87.2±6.5,the single pain score raised from6.5±3.0to20.5±4.9;the subjective evaluation results:(arthroscopic debridment group;excellent3，good12，middle3，poor0,the excellent and good rate is72.2%;duhuojisheng decoction and arthroscopic debridment group,excellent2，good11，middle4，poor1,the excellentand good rate is83.3%), the result shows that Lysholm functional score of the knee isstatistically significant,so as the JOA subjective evaluation.The results of3D gait analysis:the stride（m) in traditional Chinese medicinegroup,operation group,traditional Chinese medicine with operation group,blank controlgroup and the normal group were0.536±0.061，0.615±0.0670.681±0.0790.503±0.0470.754±0.080，the cadence（1/s）were1.065±0.1311.164±0.1391.289±0.1620.951±0.1011.581±0.118,the velocity（m/s）were0.571±0.0710.881±0.0790.966±0.0860.478±0.0431.192±0.123,the maximum-flexion of the hip（0）8.440±0.9778.588±1.0038.963±1.1118.711±0.95010.293±1.523， The maximum-flexion of the knee （0）54.343±5.46957.210±4.80858.627±6.10352.266±5.44059.529±6.740，The maximum-flexion of theankl（e0）21.012±1.96123.188±2.57124.577±2.76519.843±2.16422.771±2.119。Thereare statistically significant in stride and velocity,but there is no difference in cadence andthe maximum-flexion.Conclusion：1.The study confirmed that duhuojisheng decoction can inhibit the expression ofIL-1β、IL-6、TNF-α and MMP-3in the synovial fluid of knee joint,and have effectiveresult on KOA.2.Arthroscopic debridment can enhance Lysholm functional score of the knee,and thestride and velocity of the gait period,which indicate that Arthroscopic debridment canrelease the pain and improve the joint function.3.Duhuojisheng decoction have synergism to combine with the Arthroscopicdebridment.3.3D motion capture system can describe and analysis the gait exactly, can be usedto evaluate the lower limp functional rehabilitation.更多还原