Wang Ying, Jia Hua, Li Wen-Yuan, Guan Li-Xin, Deng Lingxiao, Liu Yan-Cui, Liu Gui-Bo
Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang 157011, P.R. China.
Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China.
Exp Ther Med. 2016 Oct;12(4):1980-1992. doi: 10.3892/etm.2016.3585. Epub 2016 Aug 10.
The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.
本研究旨在评估在大鼠坐骨神经间隙脱细胞神经同种异体移植（ANA）修复模型中，联合骨髓基质细胞（BMSC）移植和软骨素酶ABC（Ch-ABC）治疗的分子机制。将Sprague Dawley大鼠（n = 24）用作神经供体，Wistar大鼠（n = 48）随机分为以下几组：第一组，杜氏改良 Eagle 培养基（DMEM）对照组（仅用DMEM处理ANA）；第二组，Ch-ABC组（仅用Ch-ABC处理ANA）；第三组，BMSC组（仅接种BMSC的ANA）；第四组，Ch-ABC + BMSC组（先用Ch-ABC处理ANA，然后接种BMSC）。8周后，通过逆转录-定量聚合酶链反应和免疫组织化学检测再生组织中神经生长因子、脑源性神经营养因子和血管内皮生长因子的表达。通过免疫组织化学、辣根过氧化物酶逆行神经追踪、电生理和胫前肌恢复分析来检查轴突再生、运动神经元保护和功能恢复情况。观察到联合治疗增强了供体神经在局部以及远端、脊髓运动神经元和靶肌肉器官水平的生长反应。这种现象可能是由于源自移植部位的生长信号逆行和顺行运输的传播。总的来说，供体神经、靶肌肉和运动神经元的生长改善最终有助于有效的轴突再生和功能恢复。为了优化ANA后有效的治疗和完全的功能恢复，需要对分子周围神经损伤联合策略进行深入研究。
