Abstract:

Objective To explore the effects of exosomes derived from miR⁃210⁃5p⁃modified mesenchymal stem cells（MSCs）on spinal cord injury（SCI）in rats. Methods MSCs from SD rats were isolated and cultured， and were transfected with mirna⁃210⁃5p mimic or NC mimic. Subsequently，60 adult male SD rats were randomly divided into five groups with 12 rats in each group. Except the sham operation group，rats in other four groups underwent T10 laminectomy to construct SCI model. A total of 200 rats were injected with 200 μL MSCs or MSCs NC mimic or miR⁃210⁃5p exosomes or normal saline into caudal vein every day after operation for 14 days. The motor function of hind limbs was evaluated by BBB scale. The expressions of growth associated protein（GAP）⁃43， neurofilament protein（NF），Keap1 and nuclear factor E2 related factor 2（Nrf2）were detected by Western blot. The mRNA levels of heme oxygenase⁃1（HO⁃1）and quinone oxidoreductase（NQO1）were detected by RT qPCR. Results Compared with the SCI model group，the BBB score of miR ⁃ 210⁃5p secretory group was significantly higher（P < 0.05）. Further studies showed the expression of GAP⁃43 was significantly inhibited in the miR⁃210⁃5p secretory group，（P < 0.05），while the expression of HO⁃1，NF and NQO1 was enhanced（P < 0.05）. Ml385，an inhibitor of Nrf2，reversed the role of miR⁃210⁃5p secretory in SCI rats. Conclusion miR⁃210⁃5p modified MSCs derived exosomes promoted the repair of spinal cord injury in rats by activating keap1⁃nrf⁃2 pathway.

Key words:

miR ?210?5p, mesenchymal stem cells, exosomes, spinal cord injury, the Keap1? Nrf2 pathway, rats