Protective effect of dexmedetomidine on iron overload⁃induced injury of mouse hippocampal neurons
10.19405/j.cnki.issn1000-1492.2022.10.022
- Author:
Hui Ding
1
;
Jingyan Wang
1
;
Yan Huang
2
;
Weiwei Zhong
3
;
Xianfu Lu
3
;
Yuanhai Li
1
,
3
Author Information
1. Dept of Anesthesiology , Chaohu Hospital Affiliated to Anhui Medical University , Chaohu 238000
2. Anhui Provincial Laboratory of Inflammatory and Immune Diseases , Anhui Institute ofInnovative Drugs , School of Pharmacy , Anhui Medical University , Hefei 230032
3. Dept of Anesthesiology , The First Affiliated Hospital of Anhui Medical University , Hefei 230022
- Publication Type:Journal Article
- Keywords:
ferroptosis;
dexmedetomidine;
iron overload;
hippocampal neurons
- From:
Acta Universitatis Medicinalis Anhui
2022;57(10):1633-1639
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the protective effect and related mechanisms of dexmedetomidine (Dex) on iron overload toxicity in mouse hippocampal neurons (HT22) induced by ferric ammonium citrate (FAC) .
Methods:Selected HT22 cells in good condition were randomly divided into 4 groups: control group ( Ctrl group), FAC treatment group (FAC group), Dex treatment group (Dex group), ferroptosis inhibitor Fer⁃1 treatment group (Fer1 group) . The iron overload model was established by FAC⁃induced cells . Subsequently, the proliferation and survival rate of HT22 cells was detected by CCK⁃8 method; Western blot was used to detect the ferroptosis marker proteins prostaglandin⁃endoperoxide synthase 2 ( PTGS2 ) and acyl⁃CoA synthetase long⁃chain family member 4 (ACSL4) . The protein expressions of mammalian target of rapamycin ( mTOR), transferrin receptor 1 ( TFR1) and ferroportin (Fpn); the gene expression levels of PTGS2 and ACSL4 in HT22 cells were detected by qPCR; Reactive oxygen species (ROS) levels in HT22 cells was detected by DHE fluorescent probe; MDA detection kit was used to detect lipid oxidation levels in HT22 cells; Mito⁃FerroOrange—ferrous ion probe was used to detect ferrous ion levels in HT22 cells; electron microscopy was used to detect intracellular ultrastructural changes .
Results:Dex group and Fer⁃1 group significantly decreased cell death rate after 2 h of pretreatment, the protein and gene expression levels of ferroptosis markers PTGS2 and ACSL4 significantly decreased . The degree of cell ultrastructural damage was significantly improved . The levels of ROS, lipid oxidation and Fe2 + were significantly lower than those of the FAC group (P < 0. 05) .
Conclusion :Dex pretreatment can attenuate FAC⁃induced iron overload toxicity in⁃ jury in HT22 cells, which may be related to the inhibition of ferroptosis .
- Full text:2024081121483889224右美托咪定对铁超载诱导的小鼠海马神经元损伤的保护作用_丁慧.pdf