Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 1, January, p. 135–145

doi: 10.17219/acem/104556

Publication type: original article

Language: English

License: Creative Commons Attribution Non-Commercial License

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Vitexin improves neuron apoptosis and memory impairment induced by isoflurane via regulation of miR-409 expression

Yingkai Qi1,A,F, Linlin Chen1,B,C, Shiqiang Shan1,C,D, Yu Nie1,D,E, Yansheng Wang1,E,F

1 Cangzhou Central Hospital, China

Abstract

Background. Anesthetics, such as isoflurane, sevoflurane, ketamine, and desflurane, are commonly used in clinics. Specifically, isoflurane is one of the most commonly used inhalational anesthetics, which can be used in surgery patients of all ages, including children.
Objectives. The aim of the study was to investigate the mechanisms of vitexin against isoflurane-induced neurotoxicity.
Material and Methods. Reference memory testing was performed for 5 days (4 trials, 2 per day) before anesthesia. Reversal testing was performed on the 3rd day after anesthesia. The cell viability and apoptosis of PC-12 cells were detected using MTT and TUNEL assays, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum tumor necrosis factor α (TNF‑α), interleukin 6 (IL‑6), glutathione (GSH), and superoxide dismutase (SOD) concentrations. The concentration of reactive oxygen species (ROS) was detected using ROS measurement. Expression of miR-409 was determined using quantitative reverse-transcription polymerase chain reaction (qPT-PCR). Protein expression levels were detected using western blotting.
Results. Rats treated with isoflurane showed significant increases in the escape latency periods (ELP) and the apoptosis of hippocampus neuron cells; this effect was reversed by 3 mg/kg or 10 mg/kg of vitexin (p < 0.05). Further testing showed that isoflurane could significantly decrease the cell viability and increase the apoptosis of PC-12, the expression of inflammatory cytokines (TNF‑α and IL‑6) and ROS (p < 0.05). However, these results were reversed by 10/100 μM of vitexin. In addition, vitexin could significantly increase the expression of miR-409 (p < 0.05). Further studies showed that overexpression of miR-409 could significantly promote the effect of vitexin on isoflurane-induced neurotoxicity (p < 0.05). Finally, overexpression miR-409 could significantly increase the expression of p-AMPK/t-AMPK and p-GSK3β/t-GSK3β.
Conclusion. Vitexin has protective effects against isoflurane-induced neurotoxicity by targeting miR-409 and the AMPK/GSK3β pathway.

Key words

neurotoxicity, isoflurane, vitexin, miR-409, AMPK/GSK3β signaling pathway

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