Sustainable Release Selenium Laden with SiO Restoring Peripheral Nerve Injury via Modulating PI3K/AKT Pathway Signaling Pathway.

BACKGROUND

Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively.

METHODS

Se@SiO NPs were synthesized using a mixture of Cu Se nanocrystals, and the mechanism of action of Se@SiO NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO NPs for peripheral nerve regeneration were determined.

RESULTS

Porous Se@SiO was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM HO and 200 μg/mL Se@SiO, and RNA-seq revealed that porous Se@SiO was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO.

CONCLUSION

Se@SiO NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.