SeNPs Derived From Proteus Mirabilis YC801 Alleviate Oxidative Stress And Inflammatory Response To Promote Nerve Repair In Rats With Spinal Cord Injury

[Objective] Biogenic Nano-Selenium Particles（Bio-Se NPs）were prepared and their biological characteristics were identified.To investigate the biogenic selenium nanoparticles promoting the proliferation and differentiation of neural stem cells（NSCs）and related signaling pathways.To investigate the therapeutic prospect of bio-derived nano-selenium particles on spinal cord injury（SCI）in rats.[Methods] SCI is the destruction of spinal microenvironment with complex pathophysiological changes.So far,its treatment remains a challenging clinical problem.The process of spinal cord injury includes oxidative stress and inflammatory response,so this particular process determines the poor efficacy of single-target spinal cord injury drugs.Recent studies have found that antioxidant stress and anti-inflammatory are the main methods of SCI therapy at present,and inducing the proliferation and differentiation of NSCs can also promote motor function repair in rats after spinal cord injury.Nano-selenium（Se NPs）has been widely used in clinical treatment for neurotoxic and neurodegenerative diseases,and has the ability to regulate oxidative stress,inflammatory response and protect nerve regeneration.A novel Bio-Se NPs was synthesized by Proteus Mirabilis YC801.Bio-derived nano-selenium particles have the advantages of low cost,low pollution and high biocompatibility.In this study,the effects of bio-Sen Ps on the proliferation and differentiation of NSCs in different concentrations of Bio-Se NPs were observed,as well as the related signaling pathways involved.In order to further explore the improvement effect of Bio-Se NPs on the microenvironment in SCI rats,we established an impact model of spinal cord injury in rats,and injected Bio-Se NPs into SCI rats by intragastric administration.After weeks 1,2 and 4 weeks later,the blood and histological sections of the injury sites were observed and analyzed.[Results] We successfully synthesized and characterized a novel Bio-Se NPs using Proteus Mirabilis YC801.In vitro experiments showed that Bio-Se NPs significantly promoted the proliferation and differentiation of NSCs when the concentration of Bio-Sen Ps was 10 ug/ m L,especially the positive expression of nerve cells through Wnt/β-catenin signaling pathway.In vivo experiment results showed that bio-Sen Ps significantly reduced the levels of reactive oxygen species（ROS）,malondialdehyde（MDA）,macrophages of pro-inflammatory cell M1,pro-inflammatory cytokines TNF-a and IL-6 when the concentration of Bio-Se NPs was 1.0mg/kg.It can improve the expression of glutathione peroxidase（GSH-PX）,superoxide enzyme（SOD）,anti-inflammatory M2 macrophages,anti-inflammatory factors IL-4 and IL-10,improve the microenvironment after spinal cord injury,inhibit glial scar formation,and promote the repair of motor related neurons and motor function.[Conclusion] In conclusion,Bio-Se NPs have been proved for the first time to have a powerful therapeutic ability to improve the microenvironment disorder after spinal cord injury and promote the improvement of motor function in rats after SCI.This nanoparticle is a promising drug for the treatment of SCI.