周围神经Wallerian变性不同时间点对干细胞归巢的趋化作用

Chemotaxis of peripheral nerve Wallerianian degeneration at different time points on homing of stem cells

  • 摘要: 目的 观察周围神经损伤后不同时间点Wallerian变性对骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)归巢的影响。 方法 成年雄性SD大鼠72只,体质量220 ~ 250 g,按体质量编号随机分为6组(n=12),每组内再按注射细胞和药物的不同随机分为A、B两组,A组(n=6)经尾静脉注射红色荧光间充质干细胞(red fluorescence proteinbone marrow mesenchymal stem cells,RFP-BMSCs)和0.9%氯化钠注射液,B组(n=6)经尾静脉注射RFP-BMSCs和膜蛋白CXCR4特异性拮抗剂(AMD3100);所有实验动物均在无菌条件下暴露坐骨神经,并于梨状肌下缘切断坐骨神经,近端结扎,远端旷置,然后分别在坐骨神经切断后的1 d、3 d、7 d、14 d、1个月、2个月行尾静脉RFP-BMSCs+0.9%氯化钠注射液(A组)和RFP-BMSCs+AMD3100(B组)注射,并在注射后的第3天行活体成像系统观察。 结果 随着时间的延长,RFPBMSCs在发生Wallerian变性的坐骨神经中的聚集呈现先增高后降低的现象;坐骨神经Wallerian变性的早期(1 ~ 3 d),注射RFP-BMSCs+AMD3100(B组)的RFP-BMSCs聚集现象明显弱于RFP-BMSCs+0.9%氯化钠注射液(A组),其差异有统计学意义。 结论 干细胞可以向发生Wallerian变性的神经组织聚集,在不同的时间点,其归巢现象存在先增高后降低的现象;在Wallerian变性的早期,其归巢现象可能部分受到SDF-1-CXCR4轴的调控,可以被CXCR4特异性拮抗剂AMD3100所抑制。

     

    Abstract: Objective To observe the effect of peripheral nerve Wallerianian degeneration at different time points on homing of bone marrow mesenchymal stem cells (BMSCs). Methods Seventy-two adult male SD rats weighing 220-250 g were randomly divided into 6 groups (n=12) according to their weight. Each group was divided into group A and group B according to the injected cells and drugs. Rats in group A (n=6) were injected with BMSCs and saline via their tail vein and those in group B (n=6) were injected with BMSCs and AMD3100. Their sciatic nerve was cut off along the inferior border of piriformis under aseptic condition with its proximal end ligated and distal end excluded. The rats in group A were injected with BMSCs and saline 1, 3, 7, 14 days, 1 and 2 months after sciatic nerve transaction and those in group B were injected with BMSCs and AMD3100. Three days after injection, the effect of peripheral nerve Wallerianian degeneration on homing of BMSCs was observed through the in vivo imaging system. Results The aggregation of BMSCs in sciatic nerve with Wallerianian degeneration increased at fi rst and then decreased with the prolonged time, and was weaker in group B than in group A during the early Wallerianian degeneration of sciatic nerve (1-3 d). Conclusion BMSCs can migrate into the peripheral nerve tissue with Wallerianian degeneration. Their homing increases at fi rst and then decreases with time, which is regulated by the SDF-1-CXCR4 axis and inhibited by the CXCR4 speci fi c antagonist AMD3100.

     

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