首页|艾司氯胺酮对癫痫大鼠海马神经元损伤的影响

艾司氯胺酮对癫痫大鼠海马神经元损伤的影响

扫码查看
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 2 μL 和 0.9%NaCl 2 μL)、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 2 µL和RGMa慢病毒液2 μL).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/P13K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.
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.

esketaminemiRNA-142-5pepilepsyrepulsive guidance molecule-aphosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β signaling pathwayneuronal injury

赵茜娟、孟丽华、杨亚男、李雅琳、陆阳

展开 >

西安交通大学 第二附属医院 麻醉科,陕西西安 710004

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

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(21)