Research Of Neuroprotective Effects Of NRG-1 Via PI3K/Akt Pathway On Spinal Cord Injury In Rats

Spinal cord injury is a kind of disease with high morbidity and high disability rate,and the clinical treatment is not satisfactory.In recent years,the development of biotherapy has been the focus of clinical and clinical research.The direct injury of the spinal cord is usually referred to as the primary injury.Because the ischemia and hypoxia can cause environmental changes,a variety of pathological changes such as inflammation and apoptosis are called the second injury.Usually the primary injury is irreversible,the partial injury of cytokine releasing,axonal loss and glial scar formation,caused by the primary injury,is considered to be reversible.The research results of our team show that,NRG-1,the full name of Neuregulin-1,can reduce secondary injury in spinal cord injury by anti-inflammatory and anti-apoptotic effect and protect neurons after spinal cord injury.In this study,we will continue to investigate the protective mechanism of NRG-1 on neurons after spinal cord injury in rat models of spinal cord transect injury.Previous studies have shown that NRG1 can activate a series of signaling pathways following binding to its receptor ErbBs on the cell membrane.In the study of cerebral ischemia reperfusion injury,it is shown that NRG1 can activate the phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway,then activate its downstream pathway and play a protective role in the nervous system.Therefore,in this study,in the models of treatment of NRG-1 after rat spinal cord transect injury we will discuss whether the neurons are protected by the PI3K/Akt pathway,and the protective effects of NRG-1 on spinal cord injury are mainly through the participation in the intrinsic apoptotic pathway(mitochondrial pathway).The expression of Akt and p-Akt was detected by immunohistochemistry and western blot was used to detect Akt、p-Akt and Bcl-xl in each group.Bad and p-Bad was detected by ELISA.The detection of gene Akt、Bad、Bcl-xl、BAX、Cytochrome c、Apaf-land Caspase-9 was performed by quantitative real-time PCR.After Spinal cord transect injury in rat p-Akt,p-Bad and Bcl-xl was decreased.After administration of NRG-1 the expression of p-Akt、p-Bad and Bcl-xl was significantly increased and the level of genes also showed the same trend,meanwhile the use of PI3K/Akt signaling pathway inhibitor LY294002 functioned,and Bcl-xl、Phosphorylation of Akt and Bad was inhibited by LY294002.The expression levels of apoptotic molecules BAX、Cytochrome c、Apaf-1 and Caspase-9 related to the endogenous apoptotic pathway were not statistically different in the spinal cord injury group and in the NRG-1 group.These results indicate that the treatment of NRG-1 after spinal cord transect in rats can play a protective role via PI3K/Akt signaling pathway and the regulation of its downstream molecule Bad and up regulation of anti apoptotic molecule Bcl-xl.NRG-1 is not mainly involved in the protective pathway by participating in the endogenous apoptotic pathway.