Zinc Promotes Functional Recovery After Spinal Cord Injury By Activating Nrf2/HO-1 Defense Pathway And Inhibiting Inflammation Of NLRP3 In Nerve Cells

Objective The purpose of this study is to investigate the regulation of the Nrf2/HO-1defense pathway by zinc to inhibit the oxidative stress and inflammatory response of nerve cells,so as to play a protective effect on nerve function after spinal cord injury(SCI).Methods In this experiment,a mouse spinal cord injury model was established by the modified Allen’s method,and then the experimental mice were randomly divided into four groups: sham operation group(Sham),solvent group(SCI-Vehicle),zinc gluconate treatment group(SCI+ Zn G),zinc gluconate and pathway inhibitor group(SCI+Zn G+ML385).Each group was injected with control solvent,zinc gluconate(Zn G,30mg/kg)and Zn G+ML385 two hours after spinal cord injury.Then,BMS scores were used to evaluate the neurological function of mice after spinal cord injury at 1,3,5,7,10,14,21 and 28 days after operation.Next,Nissl staining and hematoxylin-eosin staining were used to observe the number of Nissl bodies and tissue morphology of the spinal cord in each group;at the same time,TUNEL staining was used to detect apoptosis in spinal cord tissue.The structure of neuronal chromatin and mitochondria was observed by transmission electron microscope(TEM).Westernblot(WB)and immunofluorescence(IF)were used to detect the expression of nuclear factor red blood cell 2 related factor 2(Nrf2)related antioxidant protein and Nlrp3 inflammation related protein in vivo and in vitro.At the same time,the expression of oxidation products in each group of spinal cord tissue was detected with related kits.Results Zinc treatment promoted motor function recovery on days 3,5,7,14,21 and 28 after SCI.In addition,zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery.At the same time,zinc reduced the levels of reactive oxygen species(ROS)and malondialdehyde(MDA)in spinal cord tissue after SCI,while increasing superoxide dismutase(SOD)activity and glutathione peroxidase(GSH-PX)production.Zinc treatment resulted in up-regulation of Nrf2/HO-1 levels and down-regulation of nlrp3inflammation-associated protein expression in vitro and in vivo.Conclusions Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3 inflammation.Potential mechanisms may include activation of the Nrf2/HO-1 pathway to inhibit nlrp3 inflammation following spinal cord injury.Zinc has the potential to treat SCI.