艾司氯胺酮对癫痫大鼠海马神经元损伤的影响  

Effects of esketamine on hippocampal neuron injury in epileptic rats

作　　者：赵茜娟 孟丽华[1] 杨亚男 李雅琳 陆阳 ZHAO Xi-juan;MENG Li-hua;YANG Ya-nan;LI Ya-lin;LU Yang(Department of Anesthesiology,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi’an 710004,Shannxi Province,China)

机构地区：[1]西安交通大学第二附属医院麻醉科,陕西西安710004

出　　处：《中国临床药理学杂志》2024年第21期3124-3129,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探究艾司氯胺酮介导微小核糖核酸-142-5p(miR-142-5p)靶向调控排斥导向分子-a(RGMa)对癫痫大鼠海马神经元损伤的影响机制。方法将SD大鼠随机分为对照组(腹腔注射0.9%NaCl)、模型组(腹腔注射3 mmol·kg^(-1)氯化锂溶液,16 h后腹腔注射50 mg·kg^(-1)毛果芸香碱溶液)、艾司氯胺酮组(在模型组的基础上,腹腔注射50 mg·kg^(-1)盐酸艾司氯胺酮注射液)、miR-142-5p mimic组(在艾司氯胺酮组的基础上,左侧侧脑室海马区注射miR-142-5p mimic慢病毒液2μL和0.9%NaCl 2μL)、RGMa组(在艾司氯胺酮组的基础上,左侧侧脑室海马区注射miR-142-5p mimic 2μL和RGMa慢病毒液2μL)。用实时定量聚合酶链反应法检测miR-142-5p和RGMa mRNA的表达水平,用蛋白质印迹法检测RGMa蛋白以及磷酸化磷脂酰肌醇-3-激酶(p-PI3K)/磷脂酰肌醇3-激酶(PI3K)、磷酸化蛋白激酶B(p-Akt)/蛋白激酶B(Akt)和磷酸化糖原合成酶激酶-3β(p-GSK-3β)/糖原合成酶激酶-3β(GSK-3β)的表达水平。结果模型组和艾司氯胺酮组的miR-142-5p相对表达水平分别为3.21±0.52和1.92±0.32,RGMa mRNA相对表达水平分别为0.54±0.09和0.81±0.11,RGMa蛋白相对表达水平分别为0.47±0.09和0.79±0.12,p-PI3K/PI3K比值分别为0.38±0.06和0.79±0.11,p-Akt/Akt比值分别为0.29±0.05和0.68±0.10,p-GSK-3b/GSK-3b比值分别为0.32±0.08和0.71±0.12,艾司氯胺酮组的上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.05,P<0.001)。结论艾司氯胺酮通过miR-142-5p靶向RGMa,调节PI3K/Akt/GSK-3β信号通路治疗癫痫大鼠的海马神经元损伤。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 2μL and 0.9%NaCl 2μL were injected into the left ventricle hippocampus),RGMa group(on the basis of esketamine group,miR-142-5p mimic 2μL and RGMa lentiviral solution 2μL 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(PI3K),phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)and phosphorylated glycogen synthase kinase-3β(p-GSK-3β)/glycogen synthase kinase-3β(GSK-3β)were detected by Western blot(GSK-3β)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-3βsignaling pathway by targeting RGMa with miR-142-5

关 键 词：艾司氯胺酮 微小RNA-142-5p 癫痫 排斥导向分子-a 磷脂酰肌醇3-激酶/蛋白激酶B/糖原合成酶激酶-3β信号通路 神经元损伤 

分 类 号：R971.2[医药卫生—药品]