【作者】 钟贵彬；

【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， 2007， 博士

【摘要】 第一部分脊髓损伤患者流行病学调查与康复训练指导【目的】更好了解脊髓损伤患者机体功能情况,特别是膀胱功能情况,并对脊髓损伤患者的康复训练给与正确指导。【方法】随机抽取上海市67名脊髓损伤患者作为志愿者,以图表形式进行流行病学调查。除基本情况以外,着重对大小便情况、尿路感染、褥疮情况以及康复锻炼等情况进行调查,其中需要通过仪器检查,则由课题组的研究人员陪同进行,这些项目包括血、尿常规检验、肾功能、B超等,其他情况则通过问卷形式完成。【结果】脊髓损伤好发于青壮年,平均年龄为45.7岁;男性占68.7%,女性占31.3%,男性多于女性;外伤占64.2%,是脊髓损伤的主要原因;胸腰段损伤占50.7%,是主要的脊髓损伤部位;仅有7.5%的患者进行较为系统的功能锻炼,有77.6%的患者未进行任何项目的功能锻炼;脊髓损伤后排尿功能障碍非常普遍,并常常导致肾功能障碍,严重影响着截瘫患者的生活质量和生存寿命。仅16.4%曾接受医生指导进行膀胱训练,未进行膀胱功能训练者占68.7%,因此我们迫切需要加强脊髓损伤患者膀胱功能训练。【结论】通过调查和分析,我们提出了综合功能训练为主,包括运动功能训练、膀胱功能训练及防褥疮训练等方面,并发症防治、辅助用具和家庭无障碍建设并重,由医生、康复工作者、残疾人工作者、工程技术人员、残疾人本人和家属共同努力,才能实现脊髓损伤患者的真正康复。第二部分脊神经吻合重建脊髓损伤后弛缓性膀胱人工反射弧的动物模型建立和远期功能研究【目的】探索利用脊髓圆锥损伤平面以上正常的脊神经根与骶神经根吻合重建膀胱神经反射通路,恢复脊髓圆锥损伤后膀胱排尿功能。【方法】对犬骶神经根进行解剖学研究,并将Beagle犬L6前根近端与S2前根远端在硬膜内显微吻合,经一段时间的轴突再生后,建立新的膀胱反射弧。神经缝合术后8个月,在制成脊髓圆锥损伤模型前后,分别进行神经电生理、膀胱肌电图及尿流动力学等远期功能研究。【结果】犬的骶神经根解剖与人类不同,犬共有3对骶神经根,以S1和S2较粗,直径在1.3mm左右,S3较细,直径在0.6mm左右。犬的泌尿系统器官主要由S1～S3脊髓节段和神经根支配,3对骶神经根对膀胱尿道的支配效能各有不同,其中S1神经根主要支配尿道括约肌,对膀胱逼尿肌的作用较少;而S2神经主要支配膀胱逼尿肌,对尿道作用较少。Beagle犬脊神经吻合术后8个月电刺激截瘫前和截瘫后2条犬左侧L6后根、神经吻合口,均可在吻合口远端记录到运动诱发电位,其波形和波幅相似;尿流动力学检查可见,当刺激开始时膀胱内压迅速上升,而腹内压增加幅度较小,刺激停止后膀胱内压迅速下降,证实膀胱内压升高是由于电刺激脊神经吻合处引起逼尿肌收缩而致。【结论】利用脊髓损伤平面以上正常的脊神经根与骶神经根吻合能重建新的膀胱神经反射通路,并使膀胱低级反射中枢上移。第三部分脊神经吻合重建SCI后弛缓性膀胱人工反射弧的HRP逆行示踪及形态学研究【目的】为了进一步探索膀胱反射弧重建的机理,为膀胱排尿中枢上移提供初步证据,我们利用辣根过氧化物酶( horseradish peroxidase,HRP)逆行示踪的方法,结合组织学方法,对通过运动神经纤维长入副交感神经纤维实现膀胱神经再支配的神经形态学机制进行初步探讨。【方法】将Beagle犬L6前根近端与S2前根远端在硬膜内显微吻合,经过轴突再生后,建立膀胱新的神经反射通路。神经缝合术后8个月,在破坏脊髓圆锥制成截瘫模型后,进行辣根过氧化物酶逆行示踪检查,吻合口的再生神经纤维光镜观察及膀胱壁组织HE染色,脊髓尼氏染色等方法观察。【结果】HRP逆行示踪显示实验侧的L6脊髓节段前角中发现HRP标记的大神经元细胞;吻合口L6前根再生的神经纤维已通过L6与S2神经根吻合端;膀胱壁细胞排列整齐、紧密,均未见明显的萎缩退变;脊髓尼氏染色显微镜下观察,可见脊髓损伤区的神经元、神经胶质细胞内尼氏体淡染,尼氏体数量明显减少甚至消失。【结论】从形态学上证实了通过L6与S2神经前根吻合建立新的膀胱神经反射通路,同时膀胱排尿中枢由骶髓上移。脊髓圆锥损伤平面以上的躯体运动神经轴突可长入膀胱平滑肌内副交感神经节细胞,并由此传递躯体反射冲动致膀胱平滑肌。第四部分脊神经吻合重建脊髓损伤后弛缓性膀胱排尿功能的临床研究【目的】临床研究脊神经吻合重建膀胱神经反射通路,恢复脊髓圆锥损伤所致弛缓性膀胱的排尿功能。【方法】根据ASIA标准选择脊髓圆锥损伤所致弛缓性膀胱患者,利用T10或T11前根与S2神经前根通过腓肠神经桥接缝合的方法,对临床7例脊髓圆锥损伤所致弛缓性膀胱的患者行单侧T10/T11与S2神经前根经腓肠神经移植吻合,经一定时间轴突再生后,通过尿流动力学、尿检及排尿情况等检测膀胱排尿功能。【结果】根据神经生长速度和神经再生长度,手术后T10或T11神经与S2神经经腓肠神经移植吻合后轴突再生所需要的时间较长,因此手术后随访时间较长。本组7例病例,2例较早开展的膀胱功能重建手术,1例女性患者在术后18个月后恢复排尿功能,每次排尿量可达到300～400毫升,能自行控制排尿,无尿潴留及尿失禁情况发生,残余尿为10～30毫升左右,尿流动力学显示排尿完全是由膀胱逼尿肌的收缩引发。另1例男性患者现术后随访4年,术前曾行膀胱造漏,术后指导行膀胱功能训练,但由于该患者出院后未能坚持膀胱功能训练,一直依赖膀胱造漏,术后4年随访膀胱功能无恢复。其余5例仍处于随访期。【结论】通过脊神经吻合重建新的膀胱反射弧,能恢复SCI患者排尿功能,实现自控性排尿。更多还原

【Abstract】 Part one A epidemiology investigation on the condition of spinal cord injury and rehabilitation exercise instruction【Objective】To survey the condition of spinal cord injury and rehabilitation exercise, which is significant to enhance and instruct the appropriate functional exercise in spinal cord injury.【Methods】Sixty-seven paraplegias consent to accept the investigation from July 2002 to December 2003.They were inquired according to the questionaire created by study group. In addition to the basic living condition ,the urination and defecation , urinary tract infection ,bedsore and rehabilitation exercise were mainly investigated .The examinations,including blood routine ,urine routine,renal function and ultrasound examination of urinary system which using some kind of apparatus, were carried out accompanied by personnel .The other condition were accomplished by answering the questionnaire.【Results】Of the spinal cord injuried patients ,the middle-age were more common and the mean age was 45.7 . The male were injuried much more easily than the female. The ratio of the male was 68.7 percent while the female was 31.3 percent .The trauma was the main cause of spinal cord injury which accounted 64.2 percent of all injury causes in these patients. The most common level of injuried spine was thoracic-lumber spine which accounted 50.7 percent. Only 7.5 percent patients had ever undertook systemic functional exercises, while patients accounted 77.6 percent had no exercises. Bladder dysfunction was most common in spinal cord injury. It usually damaged renal dysfunction and affected the quality of life and the life-expectancy. Only 16.4 percent had ever received doctor’s instruction about bladder training, 68.7 percent had never trained bladder micturition . It was obviously that we should urgent to enforce the bladder function training in spinal cord injury.【Conclusions】According to the survey and analysis ,we proposed the plan including not only paying attention to motor function training, micturition training and bedsore prevention training, but also complication prevention ,aid appliance and family no obstacle construction . With the help of doctor ,rehabilitation worker , engineering technicians and the paralysics’family ,the spinal cord injuried patients can implement the true rehabilitationPart Two Experimental modeling and long-term function study on the artificial bladder reflex arc established by spinal nerve root microanastomosis in therapy of atonic bladder after spinal cord injury【Objective】To establish the artificial bladder reflex arc by the normal body reflex pathway above the horizon of spinal cord injury to reinnervate the flaccid bladder and restore bladder micturition function.【Methods】The anatomy characteristic of sacral nerve root were observed . It is achieved by intradural microanastomosis of the L6 ventral root to S2 ventral root. After axonal regeneration ,the artificial reflex pathway was reestablished. Long-term function of the reflex arc was observed by nerve electrophysiological experiment ,detrusor electromyography experiment and urodynamic testing at 8 months’postoperation.【Results】In the canine anatomy, only three sacral nerve root innervate the pelvic cavity organ system. The diameter of S1 and S2 nerve root are 1.3mm ,but S3 nerve root is 0.6mm .For bladder innervation , S2 nerve root is most dominant,while for sphincter S1 nerve root is most dominant. Trains of the stimuli(200μV 5ms) on the left L6 dorsal root and nerve anastomosized site resulted in motor evoked potential recorded from the disal to the anastomosized site before and after the spinal cord destroyed horizontally between S1 and S4 segment level in two Beegle dogs.The figure and amplitude of the motor evoked potential were similar to the normal control and general stability which stated noninterventional wave. Urodynamic testing display quick increase of bladder pressure but minor raise in abdominal pressure .This manisfested that detrusor of bladder not abdominal muscle mainly contributed intravesical pressure rising .【Conclusions】Long-term observation of nerve electrophysiological experiment ,detrusor electromyography experiment and urodynamic testing stated that the new artificial reflex arc had been established successfully. The somatic motor axons can regenerate into the parasympathetic endoneurial tubes of autonomic nerve.Part Three HRP retrogradation tracing and morphological study on artificial reflex arc reconstructed for atonic bladder by spinal nerve root microanastomosis after spinal cord injury【Objective】To study new artificial reflex pathway established by normal reflex above the level of spinal cord injury and reinnervated by the somatic motor nerve regenerating through the spinal nerve, and to explore the neural morphological basis of the artificial bladder reflex arc how to control micturition.【Methods】It is achieved by intradural microanastomosis of the L6 ventral root to S2 ventral root . After axonal regeneration ,the new nerve pathway was established. So HRP retrograde tracing was carried out after the spinal cord was destroyed horizonally between S1 and S4 segement level at 8 months postoperative. And regenerative nerve was also observed under light microscopy. The wall of urinary bladder and terminal cone of spinal cord were respectively handled by HE dyeing and Nissl’s staining .【Results】It was seen that HRP labeled cells was found in L6 ventral horn on the experimental side under light microscopy. The regenerative nerve fiber of L6 ventral root had grown through the anastomotic site to distal nerve root. The cell of bladder wall lined up tightly in order and was no cataplasia .Nissl’s staining showed that tigroid body in neuron and neuroglia cell stained lightly ,decrease or disappear after spinal cord injury.【Conclusions】The new bladder reflex arc by spinal nerve anastomosis between L6 and S2 ventral root had been established according to the HRP retrogradation tracing and morphological observation .The micturition centre had been transferred from terminal cone of spinal cord. The somatic motor axons above the lumbosacral injuried level can innervate bladder parasympathetic ganglion cells and thereby transfer somatic reflex activity to the bladder smooth muscle.Part Four Clinical study in establishing an artificial reflex arc to restore controlled micturition of atonic bladder after spinal cord injury【Objective】To study the establishment of an new artificial bladder reflex arc for controlled micturition function in terminal cone of spinal cord injury .【Methods】Seven patients in conus medullaris injury were included by unilateral microanastomosis of the T10/T11 ventral root to S2 ventral root. After several months of axonal regeneration,the micturition function were examined clinically and urodynamically.【Results】The follow-up time were longer because of anastomotic nerve regeneration .Two patients were undertook operation more early than other cases. One female case was put on intermittent urethral catheterization and gradually began to urinate spontaneously after 18 months postoperation. The patient has been followed up for 55 months and now she does not need any urethral catheterization and able to urinate completely by herself 4~5 times one day. The urinary output is 500-800 ml one time. She has had the sensation of bladder fullness, and urinate spontaneously and powerfully without any difficulty. The results of urodynamic study showed that detrusor has nerve reflex while the external sphincter is denervated. It is thus clear that the acquired function of urination was mainly caused by detrusor contraction, rather by compressing the bladder through abdominal muscle. The male patient of two cases didn’t acquire the controlled micturition after following up four years. The other cases were following up because of later operation and nerve regeneration.【Conclusions】Establishing of an new artificial reflex arc may effective for controlled micturition in conical SCI.更多还原