精确重建体神经-植物神经反射弧实现排尿动力与阻力协调的再平衡治疗脊髓损伤后排尿功能障碍

Bladder dysfunction after spinal cord injury is a difficult problem in clinical. The reconstruction of the Xiao procedure achieves a breakthrough for spastic bladder. But at present, Xiao procedure was designed to increase the power of urination, ignoring the balance between urination power and resistance, which is contentious with widely accepted Brindley surgery. The applicant investigate the recovery of urinary dynamics and resistance balance by making best use of the advantages and bypassing the disadvantages of Xiao procedure and Brindley surgery of bilateral extradural cutting off S1 and S2 and tension-free transferring S2 and S3 ventral roots to S1 ventral root for restoring neurogenic bladder to do further exploration on the basis of the previous subject of National Natural Science Foundation of China" Extradural Transferring S2 Ventral Root to S1 Ventral Root for Restoring Neurogenic Bladder in Spinal Cord Injury." Thereby, the imbalance between urination power and resistance was rectified, and the rebalance was achieved. The pretest results of canine and human cadaver specimens preliminarily verified the hypothesis. Then the sample size will be enhanced to take deep insight into anatomical characteristics of sacral nerve roots and explore the function recovery of spastic bladder of animal by bilateral extradural tension-free transferring S2 and S3 ventral roots to S1 ventral root to reconstruct reflex arc. Then we compare the effect of reconstruction with widely used Brindley stimulation, expecting to replace the Brindley operation for bladder dysfunction after spinal cord injury to provide more economical and effective new therapies and research ideas.

脊髓损伤后膀胱功能障碍是困扰临床的难题，近来肖氏反射弧手术对治疗痉挛性膀胱取得突破，但当前方案注重增强排尿动力，而忽略排尿动力与阻力协调的平衡，与公认的Brindley术比疗效有争议。申请者在前次国自然课题《硬膜外椎管内S1与S2前后根精确吻合重建人工反射弧治疗脊髓损伤后痉挛性膀胱功能障碍》上深入探索，从恢复排尿动力与阻力协调平衡入手，拟将肖氏术和Brindley术相结合扬长避短，在硬膜外椎管内先行双侧S2和S3后根切断去传入、再行双侧S1前根与S2和S3前根双根精确吻合重建反射弧、纠正痉挛性膀胱排尿动力与阻力协调失衡状态、实现排尿动力与阻力协调再平衡。犬和人脊柱标本预实验结果良好，初步验证了假说。拟扩大样本深入研究，观察犬痉挛性膀胱模型下硬膜外椎管内双侧S1前根与S2和S3前根双根吻合反射弧重建后疗效，并与Brindley术对照，为痉挛性膀胱功能障碍提供更安全经济有效的新术式和研究思路。

脊髓损伤（SCI）目前是人类最严重的灾难性损伤之一，发病率以每年5万例的速度增加，现我国SCI病人总数超过200万人。调查表明SCI患者将膀胱功能改善作为第一康复需求，对一个完全丧失排尿功能的截瘫患者，哪怕得到一点点恢复，病人也会感觉有很大改善。因此重建脊髓损伤后病人的膀胱功能对于改善病人生活质量、降低死亡率具有重要意义。近年来体神经-植物神经反射弧（肖氏反射弧）重建技术恢复脊髓损伤后大小便（特别是小便）功能取得显著疗效，尤其对痉挛性膀胱功能障碍的疗效更为明显，但目前神经移位反射弧重建均在硬膜内进行，存在手术难度高、并发症多、前后根鉴别困难、疗效不稳定、推广困难、深入机制研究不确切（硬膜内与硬膜外神经吻合其神经生长速度、效应如何？排尿动力阻力平衡改善如何？）等问题。因此，如何找到一种神经源性膀胱简单有效的治疗方法是目前亟待解决的重点。.本研究通过动物及解剖模型发现骶神经前后根神经纤维在硬膜外椎管内无交叉，在背根神经节远方出椎间孔后前后根神经纤维才开始交叉，在背根神经节腹侧打开外膜可见前后根之间有一层疏松的结缔组织间隙，此处前后根很容易分离，可实现硬膜外椎管内S1与S2和S3前根对前根无张力下交叉吻合重建反射弧；供体与受体神经之间的距离小于两神经的长度之和，S1神经移位能十分轻松地与S2和S3神经实现吻合。为将研究成果转化到临床，项目团队进一步开展了20余例临床试验研究，结果示：患者膀胱容量较术前明显增大，随着反射弧建立并发挥作用，排尿量越来越多、残余尿量越来越少，膀胱顺应性提高，尿道及膀胱痉挛得到改善，患者的生活质量明显提高，膀胱功能恢复时间较以往硬膜内反射弧重建法提前半年左右。初步临床转化研究提示，该神经移位方法效果显著，可以极大地的恢复患者的膀胱功能，且具有较高的安全性，有望成为脊髓损伤膀胱功能障碍的主要治疗方法之一。