GABA_A Receptor/STEP61 Signaling Pathway May Be Involved in Emulsified Isoflurane Anesthesia in Rats

• Main Authors: Xingkai Zhao, Guangjun Chang, Yan Cheng, Zhenlei Zhou
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: International Journal of Molecular Sciences
• Subjects: DNA methylation; emulsified isoflurane (EISO); epigenetic; general anesthesia; ion channel protein
• Online Access: https://www.mdpi.com/1422-0067/21/11/4078
• ISSN: 1661-6596; 1422-0067

(1)<b> </b>Background: Emulsified isoflurane (EISO) is a type of intravenous anesthetic. How emulsified isoflurane works in the brain is still unclear. The aim of this study was to explore whether epigenetic mechanisms affect anesthesia and to evaluate the anesthetic effects of emulsified isoflurane in rats. (2) Methods: Rats were randomly divided into four groups (<i>n</i> = 8/group): The tail vein was injected with normal saline 0.1 mL·kg⁻¹·min⁻¹for the control (Con) group, with intralipid for the fat emulsion (FE) group, with EISO at 60 mg·kg⁻¹·min⁻¹ for the high-concentration (HD) group, and 45 mg·kg⁻¹·min⁻¹ for the low-concentration (LD) group. The consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. (3) Results: Using real-time polymerase chain reaction (PCR) to assess the promoter methylation of ion channel proteins in the cerebral cortex of rats anesthetized by EISO, we demonstrated that the change in the promoters’ methylation of the coding genes for gamma-aminobutyric acid A receptor α1 subunit (GABA_Aα1), N-methyl-D-aspartate receptor subunit 1 (NMDAR1), and mu opioid receptor 1 (OPRM1) was accompanied by the change in messenger ribonucleic acid (mRNA) and protein expression by these genes. (4) Conclusion: These data suggest that the epigenetic factors’ modulation might offer a novel approach to explore the anesthetic mechanism of EISO.