文献检索，用中文搜 PubMed

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.

BACKGROUND

METHODS

RESULTS

CONCLUSION

背景

抑制 ROS 过度产生被认为是治疗周围神经损伤的一种非常有效的策略，而硒具有显著的抗氧化作用；然而，由于硒的有效浓度和毒性剂量之间的差异不大，我们合成了一种可以缓慢释放硒的纳米材料，以便更有效地使用它。

方法

使用 CuSe 纳米晶体的混合物合成了 Se@SiO NPs，通过细胞实验进行测序、免疫荧光染色和 Western blot 初步探索了 Se@SiO NPs 的作用机制。通过动物实验后的行为学测定和材料取样进行组织学染色、免疫荧光染色和 ELISA，进一步确定了 Se@SiO NPs 的作用机制。确定了 Se@SiO NPs 对周围神经再生的作用、机制和生物相容性。

结果

成功合成了多孔 Se@SiO，具有良好的颗粒性质，并能缓慢释放硒。CCK-8 实验表明，最佳实验剂量为 100μM HO 和 200μg/mL Se@SiO，RNA-seq 表明多孔 Se@SiO 与细胞增殖、细胞凋亡和 PI3K/AKT 通路有关。WB 显示多孔 Se@SiO 可增加细胞增殖抗原（PCNA 和 S100）和抗凋亡蛋白（Bcl-2）的表达，降低促凋亡蛋白（Bax）的表达，增加抗氧化应激蛋白（Nrf2、HO-1 和 SOD2）的表达。EdU 细胞增殖和 ROS 荧光测定表明多孔 Se@SiO2 促进了细胞增殖并降低了 ROS 水平。LY294002（PI3K/AKT 通路抑制剂）的治疗效果显著降低，同时添加多孔 Se@SiO 时其效果丧失。动物实验表明，给予多孔 Se@SiO 后，再生神经纤维密度、髓鞘厚度、轴突面积、比目鱼肌湿重比、肌纤维面积、坐骨神经功能指数（SFI）、CMAP、凋亡细胞比例以及抗氧化应激蛋白和抗炎因子水平均增加。与 PNI 组相比，Se@SiO 组的氧化应激蛋白和抗炎因子水平显著升高，LY294002 的作用显著降低，同时添加多孔 Se@SiO 时其效果丧失。