【作者】 何洪波；

【导师】 李康华；

【作者基本信息】 中南大学 ， 外科学， 2007， 博士

【摘要】 脊柱功能单位（functional spinal unit，FSU）是指两个相邻椎体及其连接结构包括椎间盘、韧带、关节突和关节囊等的复合体，是代表脊柱运动的基本单位。椎间盘及后方的关节突关节共同构成三关节复合体，椎间盘是FSU的负载活动轴心。退变性椎间盘疾病是下腰痛的主要原因，传统的手术治疗包括单纯椎间盘髓核切除术及椎间盘髓核切除术同时脊柱融合，但腰椎间盘摘除术将对椎间隙高度、腰椎应力分布、节段运动及刚度等产生明显的影响，从而易导致一系列腰椎节段生理功能紊乱。脊柱融合术能有效解决病变节段的稳定与椎间隙高度维持的问题，但又将加速邻近节段的退变从而导致新的病损。所以上述两种方法都是非生理性的，使得人们不得不进一步探求解决和预防椎间盘切除和椎体融合术后各种问题的新方法。人工腰椎间盘置换术（artificial disc replacement，ADR）正是基于此目的，以期能达到重建椎间盘重要的生理功能，维持椎间隙高度、节段性稳定和节段性运动的效果。由于椎间盘是FSU的负载活动轴心，所以对腰椎间盘力学性能及其退变机理的研究对揭示腰椎相关退行性疾病的生物力学基础具有十分重要价值。研究不同术式对相邻上位椎间隙的影响对探讨腰椎间盘术后疗效的影响因素也就具有十分重要的临床意义。ADR尚未广泛应用，其对腰椎生物力学的影响报道较少，而对比研究ADR、腰椎间盘摘除、椎问融合对相邻上位椎间隙的影响尚无相应报道。本课题首先采用生物力学的方法，利用根据电测法的原理自行设计的改良圆片状微型压力传感器，测量L_4／5椎间盘完整组、椎间盘摘除组、椎间盘置换组以及椎间融合组在轴向、前屈、后伸、侧弯等不同压力或力矩载荷下，其相邻上位(L_3／4)椎间隙压力的改变，从生物力学角度研究腰椎间盘髓核摘除、ADR以及椎间融合对上位椎间盘的影响。同时，通过对L_4／5椎间盘摘除、ADR以及椎间融合三组手术病例至少3年的随访，采用JOA、VAS评分方法，比较三种不同手术方式的临床疗效；并对术前、术后6、12、24、36月X线片上L_3／4间隙出现的椎间隙狭窄、椎间隙楔形样变、骨赘形成、软骨终板钙化四种椎间盘退变异常征象频数之和进行统计，比较不同手术方式对邻近上位椎间盘退变的影响。为腰椎间盘突出症治疗方法的选择提供进一步依据。第一章腰椎椎间隙内压力的测量目的：了解轴向、侧弯、前屈、后伸载荷下L_3／4椎间隙内压力变化及自行设计的压力传感器的性能。方法：取10具新鲜完整的青壮年腰段标本，将根据应变片原理自行设计的圆片状微型压力传感器探头置入L_3／4椎间隙内，在腰椎标本上施加轴向（0～2000N）、侧弯（0～10Nm）、后伸（0～10Nm）、前屈（0～10Nm）分级载荷，测量四种载荷下L_3／4椎间隙内压力的变化。结果：随着整体腰椎负载的增加，各种工况下L_3／4椎间隙内压力也随之增大。在相同的压力载荷下，L_3／4椎间隙内压力前屈较轴向和侧弯时增大，比较结果有统计学差异，P＜0.05；后伸较轴向与侧弯降低，结果有统计学差异，P＜0.05；侧弯与轴向加载时L_3／4椎间隙内压力无明显差异，P＞0.05。并且随着负载的增加，各种工况下L_3／4椎间隙内压力变化的曲线均呈连续性。结论：本实验中根据应变片原理自行改良设计的圆片状微型压力传感器测量系统精度高，减小了误差，结果可靠，并可获取椎间隙内压力随载荷变化的连续曲线；在相同载荷下，正常腰椎椎间隙内的压力前屈时最大，后伸时最小，轴向与侧弯接近，大小介于前屈与后伸之间。第二章人工腰椎间盘置换对上位椎间隙压力影响的对比实验研究目的比较L_4／5椎间盘摘除、ADR以及椎间融合后上位椎间隙压力的改变，从生物力学角度研究三种不同的腰椎间盘突出症的治疗术式对邻近上位椎间盘的影响。方法取10具新鲜完整的青壮年腰段标本，将特制的圆片状微型压力传感器探头置入L_3／4椎间隙内，在腰椎标本上施加轴向（0～2000N）、侧弯（0～10Nm）、后伸（0～10Nm）、前屈（0～10Nm）分级载荷，分别测量各分级载荷下L_4／5椎间盘完整组、椎间盘摘除组、椎间融合组和人工椎间盘置换组L_3／4椎间隙内的压力，比较各组的压力大小，用SPSS12.0统计软件包进行统计分析，检验水准为α=0.05。结果相同载荷下相邻上位L_3／4椎间隙内的压力变化比较：（1）人工椎间盘置换组与椎间盘完整组比较，在各种工况及载荷下，L_3／4椎间隙内的压力无显著性差异（P＞0.05）。（2）椎间盘摘除组与椎间盘正常组及人工椎间盘置换组比较，在轴向≥1600N、前屈≥1200（6Nm）、后伸≥2000N（10 Nm）、侧弯≥1600N（8 Nm）时压力降低，有显著性差异（P＜0.05）；在轴向≤1200N、前屈≤800（4Nm）、后伸≤1600N（8 Nm）、侧弯≤1200N（6 Nm）时压力降低，但无显著性差异（P＞0.05）。（3）椎间融合组与椎间盘完整组及人工椎间盘置换组比较，在各种工况及负载等级下均明显升高，有显著性差异，其中轴向、侧弯、前屈加载时P＜0.01，后伸时P＜0.05。结论首次采用生物力学方法，比较人工腰椎间盘置换、椎间盘摘除、椎间融合对上位椎间隙压力改变的影响：（1）腰椎间盘摘除后相邻上位椎间隙压力降低，提示其可能导致上位腰椎节段应力分布的紊乱；（2）腰椎椎间融合后相邻上位椎间隙压力显著增大，提示其将导致上位椎间盘的应力明显集中；（3）人工腰椎间盘置换后相邻上位椎间隙压力变化与椎间盘完整时接近，提示其能有效避免上位椎间盘的应力紊乱。第三章人工腰椎间盘置换对上位椎间盘退变影响的临床对比研究目的评价ADR、椎间盘摘除和椎间融合术对于椎间盘突出症的临床疗效，探讨不同术式对相邻上位椎间盘退变的影响。方法收集1999～2004本科室采用ADR、椎体间融合、开窗术治疗的L_4／5椎间盘突出症病例各20例、总共60例患者资料。采用电话、信件预约，门诊复查相结合的随访方式进行。随访内容：所有患者手术前、手术6、12、24、36月后均进行详细的JOA、VAS评分测定；并收集同期的腰椎正侧位片，统计随访X线片上L_3／4椎间隙出现的软骨终板钙化、椎间隙狭窄、椎间隙楔形样变、骨赘形成四种异常征象的发生频数。用SPSS11.0统计软件包对患者术前术后不同时期的JOA、VAS评分比值（R）进行检验，三组内、组间两两对比采用配对T检验；检验水准均为α=0.05；对三组病例四种退变征象的发生频数之和在组间用Person x²统计量行x²检验，检验水准为α=0.05；由于本研究属于早中期随访，所以对代表早期退变征象的软骨终板钙化发生频数亦用同法单独进行检验比较。结果1．临床疗效结果：（1）三种术式术后各随访时段的JOA评分较术前都有显著提高，差异均有统计学意义，P＜0.001；（2）人工椎间盘置换组与开窗组JOA评分在6月时最高，而椎间融合组在12月时最高；（3）术后6、12月组间的比较，P＞0.05，没有统计学差异；（4）术后24月开窗组的JOA评分出现明显下降，而ADR组与椎间融合组的JOA评分保持较好，三组间比较：ADR组、椎间融合组结果均优于开窗组，差异有显著性，P＜0.05；ADR组与椎间融合组两组比较P＞0.05，结果无差异；（5）术后36月，椎间融合组的JOA评分开始出现明显下降，开窗组评分下降趋势较24月时不明显，ADR组评分仍然保持较好，组间比较，ADR组优于开窗组和椎间融合组，有显著差异P＜0.05；椎间融合组优于开窗组，结果仍有显著性差异P＜0.05。术后VAS评分结果的统计学差异与JOA评分结果相同。2．X线上L_3／4椎间隙异常征象频数之和比较：（1）术后6月、12月三组频数轻度增多，组间比较均没有统计学意义，P＞0.05；（2）术后24月、36月开窗组与融合组频数明显增加，而以融合组增加最为显著，组间比较：ADR组频数低于开窗组和融合组，P分别＜0.05和＜0.01，有显著性差异；开窗组低于融合组，P＜0.01，有显著性差异。代表早期退变征象的软骨终板钙化发生频数统计情况也显示了相同的结果。结论1．开窗术、ADR和椎间融合术治疗腰椎间盘突出症有明显的短、中期疗效。2．三种术式疗效稳定性依次为：ADR、椎间融合术、开窗术。3．首次通过对X线上椎间隙异常征象频数的统计分析方法证实ADR能有效避免相邻上位椎间盘的退变，可能是其疗效能获得长期维持的原因之一。4．椎间融合术可明显加速相邻上位椎间盘的退变，可能是影响其中远期疗效的原因之一；椎间盘摘除也可引起相邻上位椎间盘的退变，但影响程度较融合术小。更多还原

【Abstract】 Functional spinal unit （FSU） is the Complex includingintervertebral disc, ligament, articular process, articular capsule andadjacent vertebral body. It is the fundamental unit of spine motion.Intervertebral disc is the load and motion center of the FSU.Degenerationdisease of intervertebral disc is the primary cause of lower back pain.Traditionary operation includes discectomy or discectomy withfusion.But discectomy always decrease the height of intervertebral spaceand the stability of lumbar vertebrae segment; discectomy with fusionwill result in Adjacent Segment Disease（ASD）.The purpose of Artificialdisc replacement （ADR） is just to re-establish the physiologic function ofintervertebral disc.Because intervertebral disc is the load and motion center of theFSU,it is valuabal to study the mechanism of degeneration disease ofintervertebral disc.Up to now ADR is not used widely, there was fewreports about its effect to lumbar, and no corresponding reports abouteffects to adjacent disc compared among discectomy, discectomy withfusion and ADR.Wafer-shaped stress sensor was used to measure the intervertebraldisc pressure during the biomechartical test in this study. In order toreveal the correlation between the operation methods（discectomy, ADR,or intervertebral fusion）and adjacent superior intervertebral space.Theintervertebral space pressure of the L_3/4 were measured which appliedwith load of neutrality and flexion, extension, lateral bending. Thenconclude the effect on the adjacent superior disc after the differenttreatment. Furthermore the clinical cases of the discetomy, artificial discreplacement and intervertebral fusion were followed in 6, 12, 24, 36 months. The clinical result of the different treatment were evaluated, andthe relationship of the different treatment to the degeneration ofsuperior intervertebral disc were also evaluated by X ray.PART ONE: Measuremennt to intervertebral space pressureObjective: To explore the stress change in L_3/4 intervertebral spaceby biomechanical study.Methods: To explore the stress change in L_3/4 intervertebral spaceunder axial, flexion, extension, lateral bending loads by wafer-shapedstress sensor designed ourseves. All data was statistical analyzed withSPSS 11.0 for windows. Comparisons with values of P＜0.05 wereconsidered statistically significant.Results: the stress change were different in L_3/4 intervertebralspace under different kinds of loading. The pressure is higher with flexionthan with axial load and lateral bending which is higher than withextension（P＜0.05）.Conclusions: The stress change were different in L_3/4intervertebral space under different kinds of loading. Our wafer-shapedstress sensor was efficient for testing intervertebral spac pressure. PART TWO: The biomechanical research of the stresschange in superior intervertebral space after artificial discreplacementObjectives To compare the stress change of the L_3/4 intervertebralspace after L_4/5 discetomy, artificial disc replacement, and theintervertebral fusion during with the different motion condition, and toobserve the biomechanical effect on the superior intervertebral spaceMethods 10 fresh lumbar spinal specimens（L1～S2） obtained fromyoung adult cadavers, during the biomechanical measurement, specimenswere divided into integrity group, discectomy group, artificial discreplacement group and intervertebral fusion group of L_4/5. Theload（2000N） of neutrality and pure moments （10Nm） of axial, flexion,extension, lateral bending were applied on each group. The stress changeof the L_3/4 intervertebral space were measured with wafer-shaped stresssensor. Paired-samples T Test was used to detect significant changes ofthe difference in stress between the four groups after loading （α=0.05）.Results （1）Under all kinds of loading, the disectomy indicated adecrease of the stress in the L_3/4 intervertebral space compared to intactcondition, but P＜0.05 until loading was higher than a centainpoint,otherwise p＞0.05. （2）The interbody fusion resulted in significantincrease of the stress in L_3/4 intervertebral space compared to intactcondition（under axial, flexion and lateral bending loading,P＜0.001; underextension loading,P＜0.05）. （3）Under all kinds of loading,the ADRindicate no difference of the stress in L_3/4 intervertebral space comparedto intact condition（P＞0.05）.Conclusions A new human cadaver lumbar interbody fusionmodel was invented. The stress of L_3/4 after L_4/5 ADR was not changed which indicated it can maintain normal biomechanical function; Thestress decreasd after discectomy which indicated it can influence thestress distribution of adjacent segment; the fusion will increase stress inadjacent intervertebral space significantly indicated that the fusion is mostlikely to result in the stress concentration of adjacent segment.PART THREE: A clinical study of the change of thesuperior intervertebral space after artificial discreplacementObjectives To evaluate the therapeutic results among artificial discreplacement, discectomy and fusion;to fred out the relationship betweenoperation methods and the degree of degeneration on the adjacentsuperior intervertebral space in order to provide reference for operativemethod choosing and clinic prognosis.Methods 20 patients underwent uni-segment ADR, 20 patientsunderwent uni-segment disc excision, and 20 patients underwentuni-segment fusion from 1999 to 2004 with complete data were involved.All cases were followed-up more than 3 years, their clinical symptomsand signs were evaluated by the Japanese Orthopaedic Association scores（JOA） and VAS at 6 months, 12 months, 24 months and 36monthsfollow-up.The pykno of end plate calcification, intervertebral spacestenosis, osteophyma, intervertebral space Wedge shaped in L_3/4intervertebral space were recorded by X ray. All data recorded werecompared with statistical methodsResults: 1. JOA scores were much higher at any follow-up in allthree different surgical operations than those at pre-operation （P＜0.01）. 2. Group ADR and fusion had higher JOA scores than those in groupfenestration with statistical difference at 24 months follow-up, but thedifference between fusion and ADR group was no significance instatistics at that time. 3. Group ADR and fusion had higher JOA scoresthan those in group fenestration with statistical difference at 36 monthsfollow-up; the difference between fusion and ADR group was alsosignificanct in statistics. 4. JOA scores in ADR group was no difference instatistics at 36 months follow-up when comparison to those at 6 months,but decreased with time in fenestration and fusion group, which had astatistical sense. 5.Compaired the abnormal signs in L_3/4 intervertebralspace among the 3 groups:there was no different at 6 and 12 months;at 24and 36 months fusion group was much more than ADR and fenestrationgroup,p＜0.01,at the same time fenestration group was more than ADRgroup,p＜0.05.Conclusions All three surgical interventions had therapeutic butdifferent effects for LDH; the therapeutic effect of ADR is best and moststable among the three methods.The study shows that the interbodyfusion will result in the degeneration or acceleration of the degenerationin L_3/4 intervertebral space; ADR can avoid degeneration of adjacentlevel; discectomy also can result in the degeneration of adjacent superiorleve,but the degree is lower then fusion.更多还原