The effects of retinoic acid on nerve repair and PI3K/Akt signaling pathway after hypoxic-ischemic brain damage
10.3760/cma.j.cn421666-20240418-00280
- VernacularTitle:适宜浓度视黄酸对缺氧缺血性脑损伤后神经修复及PI3K/Akt信号通路的影响
- Author:
Siyu LI
1
;
Wei JIANG
1
;
Nong XIAO
1
Author Information
1. 重庆医科大学附属儿童医院康复科；国家儿童健康与疾病临床医学研究中心；儿童发育疾病研究教育部重点实验室；儿童发育重大疾病国家国际科技合作基地；儿童神经发育与认知障碍重庆市重点实验室，重庆 400010
- Publication Type:Journal Article
- Keywords:
Retinoic acid;
Hypoxia;
Ischemia;
Brain damage;
PI3K/Akt pathway
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2024;46(12):1079-1084
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe any effect of retinoic acid (RA) concentration on nerve repair and PI3K/Akt signaling after hypoxic-ischemic brain damage (HIBD).Methods:Primary cultured hippocampal neural stem cells were randomly divided into a control group, 0.5, 1, 5, 10 and 50μmol/L RA model groups and 5μmol/L RA+ PI3K inhibitor group. The RA groups and the RA+ PI3K inhibitor group were given those treatments at the appropriate concentrations on the 5th day of culture, and then all except the control group underwent cellular oxygen and glucose deprivation (OGD) on the following day. The RA+ PI3K inhibitor group was given PI3K inhibitor LY294002 2h before the OGD treatment. The cell viability of each group was detected using the CCK8 method at 12, 24 and 48 hours after the start of the OGD. Twenty-four hours later, the expression levels of RARα, PI3K, Akt, β-catenin, cyclin D1 protein and mRNA were detected using a reverse-transcription-polymerase chain reaction and western blotting.Results:The OD value of the 5μmol/L RA group was significantly higher than that of the model group 24 and 48h after the OGD, suggesting significant nerve injury repair. Also, 24h after the OGD the cell viability in the model and RA+ PI3K inhibitor groups was significantly lower than in the 5μmol/L RA group. The expressions of RARα, PI3K, cyclin D1 protein and mRNA in the 5μmol/L RA group were significantly higher than in the model group, and those of β-catenin protein and mRNA in the 10μmol/L RA group were also significantly higher than in the model group. RARα, PI3K, Akt, β-catenin, cyclin D1 protein and mRNA in the RA+ PI3K inhibitor group were significantly lower than in the 5μmol/L RA group.Conclusions:RA of appropriate concentration can up-regulate RARα expression and activate PI3K/Akt signaling and its downstream cyclin D1, thereby effectively promoting the proliferation and repair of hippocampal stem cells after OGD.
