喉返神经损伤后神经肌肉变化及再生特点研究

Degeneration and regeneration characteristics of nerves and muscles after recurrent laryngeal nerve injury

目的:观察大鼠喉返神经不同程度损伤后神经及甲杓肌变化、再生特点及其相互关系。方法:实验用SD大鼠95只,因感染死亡2只、手术死亡2只、运输途中死亡1只未计入统计外,将剩余90只大鼠分为完全损伤组(横断伤)及不完全损伤组(钳夹伤)各43例,对照组4例。造模成功后6h、12h、1d、3d、5d、1周、2周、3周及4周观察喉运动情况,甲杓肌肌电生理及病理组织学特点,喉返神经病理形态及超微结构变化特征。结果:大鼠喉返神经损伤后均即刻出现声带固定。完全损伤组未见声带活动恢复;不完全损伤组中41例于伤后2周声带活动恢复正常,另2例分别于伤后3周及4周声带活动恢复正常。完全损伤组伤后1d甲杓肌出现纤颤波,伤后4周出现神经再生电位;不完全损伤组甲杓肌于伤后2周内可观察到失神经电位,3周后肌电恢复正常。两组甲杓肌伤后4周均出现肌细胞卷曲变性、横纹溶解等失神经表现,完全损伤组随时间的延长肌萎缩逐渐加重,不完全损伤组损伤2周后肌萎缩现象开始逐渐好转。完全损伤组喉返神经损伤后,神经远端崩解变性程度较近端明显,伤后4周出现少量粗大的有髓神经纤维;不完全损伤组伤后1d有髓神经破坏最明显,随后逐渐好转,至伤后1周基本正常。完全损伤组Schwann细胞于伤后2周内出现吞噬现象,3周后开始出现不包绕神经纤维的Schwann细胞,以近端尤为明显;不完全损伤组伤后1周内可见Schwann吞噬现象,偶见凋亡及变性。炎性反应在完全损伤组更为严重,同时纤维母细胞及成纤维细胞逐渐增多,间质中胶原成分增加。结论:喉返神经完全损伤后,神经远端变性更为明显,伤后4周观察到再生神经,不完全损伤的喉返神经具有自我修复能力,结构恢复早于神经功能的恢复。Schwann细胞伤后可发挥吞噬作用,并有幼稚型出现。神经纤维崩解产物可能不是诱导巨噬细胞产生趋化作用的原因,但却加速巨噬细胞的迁移活化。

Objective：We investigated the degeneration and regeneration characteristics of nerves and muscles after different degrees of recurrent laryngeal nerve（RLN） injury, and then discussed the possible relations between them. Method： Ninety-five Sprague-Dawley（SD） rats were used in this study, 2 rats died of infection, 2 died during surgery and 1 died in transit. The rest 90 SD rats were classified as having complete injuries（transection,43 rats）, incomplete injuries（crush, 43 rats） and conrtol group（4 rats）. The characteristics of nerve injuries were evaluated by endoscopic examination, laryngeal electromyography（LEMG）, and histopathologic examination at 6 hours, 12 hours, 1 day, 3 day, 5 day, 1 week, 2 weeks, 3 weeks and 4 weeks after the injury. Result：All the vocal folds kept fixation in the completely injury group,where as 41/43 vocal folds in imcompletely injury group got normal activity 2 weeks after surgery, 1 at 3 weeks and 1 at 4 weeks. Fibrillation potentials were found 1 day after tran- section, and rennervation potentials appeared 4 weeks after transection. LEMG was normal 3 weeks after RLN was crushed. The average muscle fiber number of the left thyroarytenoid （TA） decreased with the time in the completely injury group, which increased in the second week after crush. Degeneration appeared more seriously in the distal region after transaction, and a small amount of large myelinated nerve fibers appeared at 4 weeks after injury. The most serious nerve degeneration appeared in the first day after crush, and 1 week later the ultrastruc- tures of RLN were almost normal. The phagocytosis of Schwann cells occurred within 2 weeks after injury, 3 weeks later we found the apperance of Schwann cells who did not wrap around nerve fibers, especially in the proxi- mal region. In the crush group, the phagocytosis of Schwann cells occurred within 1 week after injury, apoptosis and degeneration appered occasionally. Inflammatory response was more severe in the transection group, the num- ber of fibroblasts and collagen fibers in the mesenchy increased. Conclusion：The degeneration is more severe in the distal nerve when RLN is traversed. Nerve regeneration appears in the fourth week after RLN is traversed. Inju- ried nerve has the ability to repair itself. Schwann cells play a role in phagocytosis after injury, and immature Schwann cells are found. Nerve fiber disintegration product can accelerate the migration of macrophage activation.