Effects of esketamine on hippocampal neuron injury in epileptic rats
Objective To explore the mechanism of esketamine mediated microRNA-142-5p(miR-142-5p)targeted regulation of rejection directed molecule-A(RGMa)on hippocampal neuron damage in epileptic rats.Methods SD rats were divided into control group(intraperitoneally injected 0.9%NaCl),model group(intraperitoneally injected 3 mmol·kg-1 lithium chloride solution,16 h later intraperitoneally injected 50 mg·kg-1 pirocarpine solution),esketamine group(based on the model group,50 mg·kg-1 esketamine hydrochloride injection was intraperitoneally injected),miR-142-5p mimic group(on the basis of esketamine group,miR-142-5p mimic lentiviral solution 2 μL and 0.9%NaCl 2 pL were injected into the left ventricle hippocampus),RGMa group(on the basis of esketamine group,miR-142-5p mimic 2 μL and RGMa lentiviral solution 2 μL were injected into the left lateral ventricle hippocampus).Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of miR-142-5p and RGMa.RGMa protein expression levels,phosphorylated phosphatidylinositol-3-kinase(p-PI3K)/phosphatidylinositol-3-kinase(PI3 K),phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)and phosphorylated glycogen synthase kinase-3β(p-GSK-3 β)/glycogen synthase kinase-3 β(GSK-3 β)were detected by Western blot(GSK-3[3)levels.Results The expression levels of miR-142-5p in model group and esketamine group were 3.21±0.52 and 1.92±0.32,respectively;RGMa mRNA expression levels were 0.54±0.09 and 0.81±0.11,respectively;the relative expression levels of RGMa protein were 0.47±0.09 and 0.79±0.12,respectively;p-PI3K/PI3K levels were 0.38±0.06 and 0.79±0.11,respectively;the p-Akt/Akt values were 0.29±0.05 and 0.68±0.10,respectively;the p-GSK-3b/GSK-3b values were 0.32±0.08 and 0.71±0.12,respectively.Compared with the model group,there were statistically significant differences in the above indexes in the esketamine group(P<0.05,P<0.001).Conclusion Esketamine can regulate the PI3K/Akt/GSK-3(3 signaling pathway by targeting RGMa with miR-142-5p in the treatment of hippocampal neuron injury in epileptic rats.