【作者】 徐镇；

【导师】 侯春林； 陈爱民； 张伟；

【作者基本信息】 第二军医大学 ， 外科学， 2010， 博士

【摘要】 第一部分大鼠正常单根腰骶神经根切断动物模型的探讨[研究目的]对大鼠的骶丛神经根结构进行解剖学研究,同时分析其对下肢各肌群的支配权重,并通过对不同的建模方法进行比较,探讨大鼠切断单根腰骶神经根的理想模型。[研究方法]1、雄性SD大鼠10只,体重250-300g,由复旦大学动物实验中心提供,所有大鼠均采用活体处死后,咬除椎板暴露脊髓和神经根,进行解剖学的观察；2、另取SD大鼠10只,麻醉后在椎管外分别暴露出L4、L5、L6神经根,并分离出约0.5cm的一段,做刺激电极的安放位置。然后做大腿外侧纵切口,向下延伸至踝部,分别暴露股二头肌、胫前肌和小腿三头肌,将记录电极置于股二头肌肌腹,刺激电极分别置于L4、L5、L6神经根,记录复合肌肉动作电位最大波幅,同样方法分别记录小腿三头肌和胫前肌的相应数据；3、SD大鼠9只,每3只为一组,分别采用椎管外和椎管内暴露和切断神经根的方法,另取3只在椎管外暴露并切断所有L4、L5、L6神经根,以检测切断方法的可靠性。[结果]1、对10只大鼠的骶丛分别进行解剖发现,大鼠的骶丛组成主要可以分成三种类型：(1)L4、L5为主型,L6参与一小支,共有7只,(2)L4、L5型,L6不参与,共有2只,(3)L4、L5、L6共同参与型,共有1只,三种类型中,L4均为部分参与(与人类相似,其另一分支参与腰丛的组成)。2、通过对复合肌肉动作电位波幅分析,在小腿三头肌的支配中,L5的支配比重最大,其次是L4,而L6的支配比重变异较大,但也占有明显的地位；对胫前肌的支配中,主要为L4和L5神经根,其中L5的比重略大,而L6神经根的比重很小；而在股二头肌的支配中,仍为L5的比重最大,其次为L4,L6的比重最小,但与其他两根的差异不是非常明显。2、椎管内暴露法手术难度大,易损伤脊髓及马尾,并且出血较多,大鼠死亡率高,椎管外法相对简单、损伤小,并且切断可靠。[结论]大鼠骶丛神经根结构与人类有一定相似性,可以作为切断单根腰骶神经根对下肢功能影响的动物模型,而在椎管外暴露并切断神经根的方法是一种简单有效的方法。第二部分大鼠正常单根腰骶神经根切断对下肢功能影响的实验研究[研究目的]对SD大鼠切断单根正常腰骶神经根切断对下肢功能影响的动物模型进行研究,以探讨临床利用正常腰骶神经根重建脊髓损伤后弛缓性膀胱功能的可行性。[研究方法]分别建立单根L4、L5、L6神经根切断动物模型,以不切断骶丛神经根的大鼠作为对照,术前、术后及4、8、12周后分别检测下肢神经电生理,同时在4、8、12周时对实验组和对照组分别做坐骨神经功能指数测定及行为学观察,最后在12周后将大鼠处死取材,进行肌肉湿重、组织形态学及电镜观察,以评价对下肢运动功能的影响。[结果]4组大鼠术前及术后坐骨神经功能指数、复合肌肉动作电位等均无显著差异,说明4组大鼠术前具有一致性,并且神经根切除术后其坐骨神经段仍具有正常功能,而术后4周时,复合肌肉动作电位显示B、C两组坐骨神经功能显著低于A、D两组,主要表现在平均潜伏期的延长,而术后8周和12周时,其平均潜伏期逐渐恢复,4组无显著性差异；坐骨神经功能指数在术前、术后4周、术后8周、术后12周时A组对照组均大于其余3组,但其差异并不显著,并且其差异随着时间的延长而逐渐变小,由于坐骨神经指数是坐骨神经和下肢运动功能的重要参考,因此该结果提示,在各组神经根切断后,坐骨神经和下肢功能受到一定影响,但影响并不显著,而且随着时间的延长,影响也逐渐变小；而术后肌肉湿重显示各实验组肌肉均小于对照组,但差异也并不显著,仅有个别样本出现显著下降；术后组织形态学及结缔组织百分比、电镜检测均发现,从总体而言,A-D各组均无显著性差异,仅有个别实验组样本肌细胞出现明显退变。[结论]在SD大鼠实验中,我们认为,利用单根正常骶丛神经根作为动力神经进行移位修复手术是安全可行的,该方法可以用于膀胱功能重建手术,同时,该动力神经也可以用于下肢其他功能的重建。鉴于SD大鼠和人类存在一定的差异性,该方法用于临床时,需在病人完全知情同意的情况下谨慎进行。第三部分利用正常单根腰骶神经根重建弛缓性膀胱的临床研究[研究目的]在动物实验成功的基础上,研究对临床脊髓损伤后呈弛缓性膀胱而下肢运动功能正常的患者,利用其支配下肢运动功能的正常腰骶神经根,建立体神经—脊髓中枢—膀胱人工反射弧来重建膀胱功能。[研究方法]对29例脊髓损伤后下肢运动功能存在而膀胱功能障碍的病人,利用其支配正常运动功能的腰骶神经根,通过椎管内神经根切断吻合的方法,并对比手术前后肌力、肌电图、排尿情况、尿流动力学等进行对比研究。[结果]除1例病人由于椎板外粘连严重,同时咬除椎板后出血较多,仅做椎板减压和硬膜外松解外,其余28例均成功进行膀胱人工反射弧重建手术。术后第二天所有病人均检查下肢相关肌力,发现仅6例病人相关肌力轻微下降约半级,其余均无明显变化,而术后两周检查肌电图显示,3例使用L4作为动力神经的患者手术后肌电图腓总神经波幅都有降低；1例使用L5作为动力神经的患者术后肌电图也显示腓总神经波幅降低；而24例使用S1作为动力神经的患者中,有6例患者其胫神经波幅较术前下降,3例患者其胫神经、腓总神经波幅均下降,其余15例患者均表现为手术侧腓总神经最大波幅下降,另外一例仅行椎板减压及马尾神经松解病人肌电图无明显改变。术后长期排尿情况随访,20例病人排尿情况得到不同程度改善,排尿量明显增加,而残余尿均可控制在50ml以内,在其他9例患者中,除1例失访之外,在改善不明显的病人中,有3例病人虽然仍用腹压排尿,但感觉排尿所需力量较术前减小,不过残余尿都大于100ml,所以其效果仍属于较差,另外3例病人自觉排尿情况没有任何改善,因此对治疗效果并不满意。还有2例病人由于随访时间过短,排尿情况尚无改善。[结论]总体来看,利用单根支配下肢运动功能的正常腰骶神经根重建弛缓性膀胱功能,不仅是安全的,而且疗效也是比较好的。第四部分腰骶神经根间代偿机制的初步研究：猕猴下肢肌肉神经根支配分布规律的实验研究[研究目的]研究猕猴腰骶丛神经根对下肢肌肉支配的分布规律,从而探讨其神经根间的代偿机制,以作为人类神经根间代偿机制的参考。[研究方法]通过对猕猴腰骶丛神经根进行解剖学研究,并分别对下肢各个主要肌肉相对每个神经根的复合肌肉动作电位波幅进行检测,从而分析腰骶神经根对每块肌肉的支配权重。[结果]刺激腰骶神经根可于其支配的肌肉记录到复合肌肉动作电位,其波幅和时限反映的是所测的神经纤维数量和同步兴奋的程度,它与兴奋的神经纤维数量成正比,通过波幅的大小,可大致估计出执行功能的神经和肌肉的总量。因此通过本文所得到的数据可以分析猕猴L3-S1神经根对下肢肌肉支配的分布规律,从数据中我们可以看出,在下肢的几组肌肉都有显著的神经根重点支配,股四头肌以L4为首,股二头肌以L6为首,腓肠肌以L7为首,胫前肌以L5为首,趾长伸肌以L6为首,这些神经根在相应的肌肉中其波幅居于最高,但其相邻的神经根也有一定的支配比重,而间隔一个神经根的话,其虽然也有支配,但支配比重会明显下降。[结论]猕猴腰丛是由L3-L5组成,而骶丛是由L5-S1组成。猕猴下肢每组肌肉均有显著的重点神经根支配,而其相邻神经根都有一定的支配比重,因此通常每块肌肉都有三根以上的神经根参与支配,因此如果一根腰骶神经根被切断,对其产生代偿作用的主要是与其相邻的神经根,而相隔神经根的代偿作用很小,其代偿机制可能主要是神经根间交互支配产生的。更多还原

【Abstract】 Investigation of severing one nerve root of the sacral plexus in animal model:an experimental study in ratsPurpose:To observe the structure of sacral plexus in SD rats,and analysis weight of every nerve root dominating to the muscle of lower limbs.Then compare different methods of modeling, and find which one is better.Methods:1.Ten SD rats, weighing from 250g to 300g,which were provided by animal experiment center of Fu Dan university.All of rats were dissected after put to death.2. Ten SD rats,being exposed the L4,L5 and L6 nerve root to pace the stimulating electrode,then the recording electrodes were located in the triceps surae muscle, anterior tibialis muscle and biceps femoris after being exposed to record the compound muscle action potentials.3. Nine SD rats,being severed the nerve root of sacral plexus in the spinal canal,or out the spinal canal.Then study which method was better and dependable.Results:1.Three types of sacral plexus were found:(1)mainly composed of L4 and L5,with a little branch of L6.(2)Composed of L4 and L5.(3)composed of L4,L5 and L6.2. Analysis the CMAP, the triceps surae muscle was chiefly dominated by L5,then L4 and L6, anterior tibialis muscle was chiefly dominated by L4 and L5,with little dominated by L6, biceps femoris was chiefly dominated by L5,then L4 and L6.3. Severed the nerve root of sacral plexus out the spinal canal was a batter method.Conclusion:Consider the similarity between the sacral plexus of rat and of human, the model of rat was feasible to study the influence of severed one nerve root of sacral plexus, and to expose and sever the nerve root, the method of operating out the spinal canal was a batter method. The effect on lower extremity function of severing one nerve root of the sacral plexus: an experimental study in ratsPurpose:Recovery of bladder function is important in patients with conus medullaris injury. The effects of severing the S1 nerve root, to recover atonic bladder function, on motor function of the lower extremities require investigation.Methods:Forty adult male Sprague-Dawley (SD) rats were randomized into groups of 10 rats by severing the right L4, L5 and L6 nerve root, respectively, (groups B, C and D; control group A). Pre-and 4-week,8-week and 12-week postoperative electromyograms (EMGs) of the lower extremities were compared. Sciatic Functional Index (SFI), muscle weight, histological examination, and ultrastructure of the target muscle and motor end plate (MEP) were examined.Results:Relative to controls, effects were apparent in EMG at four weeks after L4 or L5, but not L6, was severed, and declined at 8 and 12 weeks. In SFI, there was a small decrease at 4 weeks, but the change was not significant or persistent. Similar results were found for muscle wet weight, except for several samples. By electron microscopy, histological examination and analysis of fiber components, we also observed significant degeneration in only a few muscle samples.Conclusion:Severance of one of the normal sacral plexus nerve roots in SD rats was feasible and did not markedly impact on lower limb motor function. Severing normal lumb and sacral anterior nerve root to reconstruct the atonic bladder function:clinical observationPurpose:At the base of animal experiment,to reconstruct function of bladder for patient with bladder dysfunction and normal function of the lower extremities by using normal lumb and sacral nerve root.Methods:In 29 patients with bladder dysfunction due to spinal cord injury and preservation of motor function of the lower extremities, the central end of normal lumb and sacral nerve root on the unaffected spinal segment was anastomosed with the peripheral end of S2 (or S3) anterior nerve root that dominates the bladder to establish a new artificial bladder reflex arc in an attempt to recover the bladder function. Differences in motor function and electromyogram of the involved parts of the lower extremities were observed. After the operation the bladder funtion was followed up,which include rinary output, residual urine, urinary tract infection and life quality.Results:Six patients who had normal lumb and sacral nerve root severed subjectively reported a sensation of slightly decreased strength of the lower leg after operation. Postoperative physical examination showed that ankle plantar flexor muscle strength(MRC scale) decreased by 0.5 degree. Electromyogram of lower limb showed that sixteen amplitudes of common peroneal nerve, six amplitudes of tibial nerve, three mplitudes of common peroneal nerve and tibial nerve were decreased. Twenty patients had improvements of bladder functions with more volume of micturition and less residual urine. Other nine patients had no obviously improvement.Conclusion:Severing normal lumb and sacral anterior root can reconstruct the atonic bladder function safely and efficiently. Primary study of the mechanism of compensation between lumbar or sacral roots:an experiment in macaques to study the nerve domination rule of muscles in lower limbsPurpose:To observe the structure of sacral plexus in macaque, and analysis weight of every nerve root dominating to the muscle of lower limbs.Then investigate mechanism of compensation between the nerve roots.Methods:the macaques were dissected to observe the structure of sacral plexus, and then four macaques were exposed the L3,L4,L5,L6,L7 and S1 nerve root to pace the stimulating electrode, then the recording electrodes were located in the quadriceps femoris muscle, biceps femoris, triceps surae muscle, anterior tibialis muscle and long extensor muscle of toes to record the compound muscle action potentialsResults:Analysis weight of every nerve root dominating to the muscle of lower limbs by CMAP. We found that each muscle was dominated by a intensive nerve root. The quadriceps femoris muscle was dominated mainly by L4. The biceps femoris was dominated mainly by L6. The triceps surae muscle was dominated mainly by L7. The anterior tibialis muscle was dominated mainly by L5. The long extensor muscle of toes was dominated mainly by L6. However the nerve roots neighboring also participate in the domination.Conclusion:lumbar plexus of macaques were composed by L3-L5,and the sacral poexus were composed by L5-L7. Each muscle was dominated by a intensive nerve root. But the nerve roots neighboring also participate in the domination, the number of which were two and more.更多还原