大鼠脊髓损伤后脊髓切开术的手术时机及机制研究

After spinal cord injury, hemorrhage and edema ensuing expeditiously are the key initiate factors which start the secondary injury, plus dura matter's bondage, neural tissue may be in the high-pressure status. Only bony decompression through removing the bone slice cannot prevent hemorrhage and swelling within the spinal cord, and also cannot relieve the high-pressure status within spinal cord. Domestic and abroad researches have been reported that myelotomy has some positive effect on spinal cord injury, but there were no mechanism researches about this operation method, and lack of related researches about operation time window. Now this study intends to build the rat thoracic spinal cord contusion model and obtain the changes of hemorrhage,swelling and intramedullary pressure with time through detecting hemorrhage volume and swelling extent with visual imagine technology and intramedullary pressure changes with micro-catheter technology.The optimal operation time is determined according to the observations of behavior,electrophysiology and histopathology aspects. The mechanism of myelotomy is explored from acute stage observation (hemorrhage, swelling, pressure) and chronic stage observation(scar formation, Nogo A, residual white matter demyelination). This study uses the initiating factors of secondary injury as entry point to investigate the surgical timing and mechanism of myelotomy in the treatment of spinal cord injury, which will provide the theoretical basis for clinical practice.

脊髓损伤后髓内出血、水肿迅速发生，是启动继发性损伤的重要起始因素，加上硬脊膜的束缚可能使神经组织处于高压力状态。而目前骨科手术不能阻止髓内出血、水肿的发展，也不能缓解脊髓内部的压力。国内外研究表明脊髓切开术对脊髓损伤有一定疗效，但无作用机制研究，而且缺乏手术时机研究。本研究分为三方面内容：一，构建大鼠胸髓挫伤模型，通过影像可视化技术测量出血体积、水肿范围以及微导管技术测量脊髓内压力，获取脊髓损伤急性期出血、水肿、压力的时间对应变化规律；二，进一步从行为学、电生理、组织病理学等方面确定脊髓切开术的最佳手术时机；三，从出血、水肿、压力的急性期观察和瘢痕形成、NogoA、残存白质脱髓鞘的慢性期观察两个方面，阐明脊髓切开术治疗脊髓损伤的作用机制。本研究以脊髓损伤后继发性损伤的始动因素控制为切入点，探讨脊髓切开术的手术时机和作用机制，为脊髓损伤的临床手术治疗提供基础理论依据。

脊髓损伤后髓内出血、水肿迅速发生，是启动继发性损伤的重要起始因素，加上硬脊膜的束缚可能使神经组织处于高压力状态。而目前骨性减压手术不能阻止髓内出血、水肿的发展，也不能缓解脊髓内部的压力。国内外研究表明脊髓切开术对脊髓损伤有一定疗效，但无手术原理研究，而且缺乏手术时机研究。本项目包含四部分，首先研究了大鼠胸髓损伤后脊髓水肿程度、髓内压力随时间的变化规律，发现脊髓水肿在损伤后2天最严重，而髓内压力在短时间内升高，之后随时间波动变化、在伤后1小时和48小时达到两个高峰（轻、中度损伤），或持续处于高值状态（重度损伤），损伤程度越严重髓内压力越高；其次，进行了脊髓切开术治疗大鼠急性脊髓损伤的手术效果及手术时机研究，证实了脊髓切开术能明显改善大鼠的运动功能恢复，初步确定最佳时间窗可能在伤后8小时至24小时；然后进一步研究了脊髓切开术对损伤脊髓组织水肿、微循环及细胞自噬水平的影响，发现脊髓切开术可通过减轻脊髓组织水肿、抑制自噬过度激活、改善局部微循环发挥神经保护作用；最后研究了脊髓切开术对犬脊髓损伤预后的影响，设计出一种新型犬脊髓打击器，并在大动物脊髓损伤模型上验证脊髓切开术的效果。本项目在动物实验中进一步阐释了脊髓损伤的继发性损伤机制即脊髓切开术的手术原理，初步确定了脊髓切开术的手术时机，证实了脊髓切开术的手术效果，为脊髓损伤的临床手术治疗提供了基础理论依据。