1. Propofol inhibited apoptosis of hippocampal neurons in status epilepticus through miR-15a-5p/NR2B/ERK1/2 pathway
- Author
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Haiming Guo, Huaping Zhao, Jiefeng Geng, Xing Liu, and Yanqiu Ai
- Subjects
0301 basic medicine ,MAP Kinase Signaling System ,Down-Regulation ,Apoptosis ,Status epilepticus ,Pharmacology ,Hippocampal formation ,Biology ,Transfection ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Flow cytometry ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Status Epilepticus ,Western blot ,medicine ,Animals ,Molecular Biology ,Propofol ,Cells, Cultured ,Neurons ,medicine.diagnostic_test ,Pilocarpine ,Cell Biology ,Rats ,Up-Regulation ,ERK1-2 Pathway ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,Mechanism of action ,nervous system ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Lithium Compounds ,medicine.symptom ,Anesthetics, Intravenous ,Developmental Biology ,medicine.drug ,Research Paper - Abstract
Although a previous study reported that propofol had a therapeutic effect in status epilepticus (SE), the mechanisms underlying the effect of propofol in SE remain unclear. The aim of this study was to explore the regulatory mechanisms underlying propofol-induced inhibition of SE. A rat SE model was established using the lithium–pilocarpine injection method. A qRT-PCR and Western blot were utilized to detect the expression of relative molecules. Cell apoptosis was evaluated by a flow cytometry assay. The interaction between miR-15a-5p and NR2B was assessed using a luciferase reporter assay. Propofol inhibited cell apoptosis and increased miR-15a-5p expression both in hippocampal tissues of SE rats and low Mg(2+)-induced hippocampal neurons. Propofol-induced attenuation of apoptosis of low Mg(2+)-induced hippocampal neurons was mediated by miR-15a-5p. miR-15a-5p targeted NR2B and negatively regulated its expression. Propofol downregulated NR2B expression, mediated by miR-15a-5p. In terms of the mechanism of action, propofol suppressed the apoptosis of Mg(2+)-induced hippocampal neurons through the miR-15a-5p/NR2B/ERK1/2 pathway. In vivo experiment suggested that propofol inhibited the apoptosis of hippocampal neurons in SE rats by upregulating miR-15a-5p. In terms of the molecular mechanism of propofol, it appears to inhibit apoptosis of hippocampal neurons in SE through the miR-15a-5p/NR2B/ERK1/2 pathway. The findings provide theoretical support for propofol treatment of SE.
- Published
- 2020