中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (2): 328-338.doi: 10.4103/1673-5374.244796

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

褪黑素联合软骨素ABC促进臂丛神经根性损伤后的神经再生

  

  • 出版日期:2019-02-15 发布日期:2019-02-15

Melatonin combined with chondroitin sulfate ABC promotes nerve regeneration after root-avulsion brachial plexus injury

Wen-Lai Guo 1 , Zhi-Ping Qi 2 , Li Yu 3 , Tian-Wen Sun 4 , Wen-Rui Qu 1 , Qian-Qian Liu 1 , Zhe Zhu 1 , Rui Li 1    

  1. 1 Department of Hand Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, China
    2 Department of Orthopedics, the Second Hospital of Jilin University, Changchun, Jilin Province, China
    3 Department of Ophthalmology, the Second Hospital of Jilin University, Changchun, Jilin Province, China
    4 Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
  • Online:2019-02-15 Published:2019-02-15
  • Contact: Rui Li, MD, PhD, 13304321102@qq.com; Zhe Zhu, MD, zhuzhe1983@126.com.

摘要:

臂丛神经根性撕脱损伤后的氧化损伤、炎症反应、胶质瘢痕形成一系列过程都会影响神经再生和功能恢复,褪黑素(MT)被证明具有良好的抗炎、抗氧化和神经保护作用。硫酸软骨素ABC(ChABC)被证明可以分解硫酸软骨素蛋白聚糖,具有减少胶质瘢痕形成的作用。但是单独使用上述一种药物改善伤后的神经功能效果都尚不令人满意。为此,作者实验设计方案联合应用MT和ChABC,观察其对臂丛神经根性撕脱后的神经再生和功能恢复的作用和机制。选择52只SD大鼠,将C5-7神经根撕脱后,对C6神经根进行回植,构建臂丛神经根性撕脱伤回植模型。建模成功后随机分为4组,损伤组采用单纯的凝胶海绵载体神经根周围植入和乙醇生理盐水腹腔注射,MT组采用褪黑素腹腔注射,ChABC组采用ChABC局部给药,MT+ChABC组采用褪黑素腹腔注射+ChABC局部给药。损伤后2-6周运动功能采用上肢Terzis理毛行为测试(Terzis grooming test,TGT)评价。损伤24 h内炎症和氧化损伤情况采用分光光度法评价。损伤后6周各组胶质瘢痕、神经元保护和神经再生情况采用免疫荧光、神经电生理法评价。结果表明,与损伤组相比,其他3组TGT评分显著提高;C5-7脊髓节段内髓过氧化物酶,丙二醛含量下降;C6脊髓节段内胶质瘢痕减少,神经元含量增加;肱二头肌内运动终板面积增大、结构清晰;肌皮神经-肱二头肌肌肉神经复合电位潜伏期最短,MT+ChABC组上述各项指标均优于MT组和ChABC组。上述结果表明,MT联合ChABC能够促进臂丛神经根性撕脱损伤后的神经再生,这可能是通过降低损伤区氧化损伤和炎症反应及抑制胶质瘢痕形成而实现。

orcid: 0000-0002-3494-9076 (Wen-Lai Guo)
           0000-0002-9922-4308 (Rui Li)
           0000-0003-1900-3044 (Zhe Zhu)

关键词: 神经损伤, 移行区, 硫酸软骨素蛋白多糖, 星形胶质细胞, 运动神经元, 硫酸软骨素蛋白多糖, 氧化损伤, 炎症反应, 胶质瘢痕, 神经再生

Abstract:

After nerve-root avulsion injury of the brachial plexus, oxidative damage, inflammatory reaction, and glial scar formation can affect nerve regeneration and functional recovery. Melatonin (MT) has been shown to have good anti-inflammatory, antioxidant, and neuroprotective effects. Chondroitin sulfate ABC (ChABC) has been shown to metabolize chondroitin sulfate proteoglycans and can reduce colloidal scar formation. However, the effect of any of these drugs alone in the recovery of nerve function after injury is not completely satisfactory. There¬fore, this experiment aimed to explore the effect and mechanism of combined application of melatonin and chondroitin sulfate ABC on nerve regeneration and functional recovery after nerve-root avulsion of the brachial plexus. Fifty-two Sprague-Dawley rats were selected and their C5–7 nerve roots were avulsed. Then, the C6 nerve roots were replanted to construct the brachial plexus nerve-root avulsion model. After successful modeling, the injured rats were randomly divided into four groups. The first group (injury) did not receive any drug treatment, but was treated with a pure gel-sponge carrier nerve-root implantation and an ethanol-saline solution via intraperitoneal (i.p.) injection. The second group (melatonin) was treated with melatonin via i.p. injection. The third group (chondroitin sulfate ABC) was treated with chondroi¬tin sulfate ABC through local administration. The fourth group (melatonin + chondroitin sulfate ABC) was treated with melatonin through i.p. injection and chondroitin sulfate ABC through local administration. The upper limb Terzis grooming test was used 2–6 weeks after injury to evaluate motor function. Inflammation and oxidative damage within 24 hours of injury were evaluated by spectrophotometry. Immunoflu¬orescence and neuroelectrophysiology were used to evaluate glial scar, neuronal protection, and nerve regeneration. The results showed that the Terzis grooming-test scores of the three groups that received treatment were better than those of the injury only group. Additionally, these three groups showed lower levels of C5–7 intramedullary peroxidase and malondialdehyde. Further, glial scar tissue in the C6 spinal segment was smaller and the number of motor neurons was greater. The endplate area of the biceps muscle was larger and the structure was clear. The latency of the compound potential of the myocutaneous nerve-biceps muscle was shorter. All these indexes were even greater in the melatonin + chondroitin sulfate ABC group than in the melatonin only or chondroitin sulfate ABC only groups. Thus, the results showed that melatonin combined with chondroitin sulfate ABC can promote nerve regeneration after nerve-root avulsion injury of the brachial plexus, which may be achieved by reducing oxidative damage and inflammatory reaction in the injury area and inhibiting glial scar formation.

Key words: nerve regeneration, nerve injury, transitional zone, chondroitin sulfate proteoglycan, astrocyte, motor neuron, oxidative damage, inflammatory response, glial scar