肿瘤坏死因子α拮抗剂联合酪氨酸激酶C基因修饰神经干细胞移植治疗脊髓损伤

发布时间：2018-04-04 18:23

本文选题：组织工程　切入点：脊髓损伤　出处：《中国组织工程研究》2017年21期

【摘要】：背景:脊髓损伤在控制损伤后炎症反应的同时联合神经干细胞移植,是否能够提高脊髓损伤的治疗效果,目前尚不明确。目的:实验旨在检测早期应用肿瘤坏死因子α拮抗剂Etanercept联合酪氨酸激酶C基因修饰移植治疗后大鼠脊髓组织修复,髓鞘再生和神经轴突再生,运动功能恢复情况及其可能机制。方法:利用慢病毒转染技术构建酪氨酸激酶C过表达的神经干细胞,制备大鼠脊髓横断损伤模型,采用肿瘤坏死因子α拮抗剂Etanercept联合酪氨酸激酶C基因修饰神经干细胞移植。利用尼氏染色、免疫荧光及免疫印迹等方法测定损伤后神经元数目和神经再生情况;利用BBB功能学评分和诱发电位来检测大鼠运动功能;利用电镜检测和甲苯胺蓝染色来检测治疗后各组髓鞘再生情况。结果与结论:损伤后28 d,与其他组相比,Etanercept联合酪氨酸激酶C-神经干细胞移植组损伤脊髓尾端处有更多前角运动神经元存活(P0.05),具备髓鞘包绕的轴突数量增高(P0.05),损伤后运动功能评分相对更高(P0.05),运动诱发电位的振幅恢复更大(P0.05),潜伏期相对更短(P0.05)。结果证实,大鼠脊髓损伤后早期应用肿瘤坏死因子α拮抗剂联合酪氨酸激酶C-神经干细胞移植,可有效促进大鼠神经元轴突及髓鞘再生,进而促进运动功能恢复。
[Abstract]:Background: it is not clear whether spinal cord injury (sci) can improve the therapeutic effect of spinal cord injury (sci) by combining with neural stem cell transplantation (NSCT) in order to control the inflammatory response after spinal cord injury (sci).Aim: to detect the recovery of spinal cord tissue, myelin regeneration and axon regeneration, motor function recovery and its possible mechanism after early transplantation of tumor necrosis factor 伪 antagonist Etanercept combined with tyrosine kinase C gene modification in rats.Methods: neural stem cells (NSCs) with tyrosine kinase C overexpression were constructed by lentivirus transfection technique. The spinal cord transection injury model was established in rats. Etanercept combined with tyrosine kinase C gene as tumor necrosis factor 伪 antagonist was used to modify neural stem cells.The number of neurons and nerve regeneration after injury were measured by Nissl staining, immunofluorescence and Western blotting, and the motor function of rats was measured by BBB functional score and evoked potential.The myelin regeneration after treatment was detected by electron microscopy and toluidine blue staining.Results and conclusion: 28 days after injury, compared with other groups, Etanercept combined with tyrosine kinase C- neural stem cell transplantation group had more anterior horn motoneurons surviving at the end of spinal cord injury than other groups, and the number of axons with myelin sheath was increased (P0.05) and injured.The score of motor function was higher than that of P0.05, the amplitude of motor evoked potential was larger than that of P0.05, and the latency was shorter than that of P0.05.The results showed that the early application of tumor necrosis factor 伪 antagonist combined with tyrosine kinase C- neural stem cell transplantation after spinal cord injury in rats could effectively promote the regeneration of axon and myelin sheath of rat neurons and then promote the recovery of motor function.
【作者单位】：中山大学附属第一医院脊柱外科;广东省骨科学重点实验室;中山大学附属第一医院东院康复科;
【基金】：国家自然科学基金面上项目(81272007) 广东省自然科学基金项目(2016A030313213)~~
【分类号】：R651.2

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