Synergistic Effects of ERK1/2 and PI3-K Pathway Inhibitors on Autophagy in the Hippocampus of Rats with Subarachnoid Hemorrhage
10.12007/j.issn.0258-4646.2017.11.008
- VernacularTitle:ERK1/2和PI3-K通路抑制剂对蛛网膜下腔出血大鼠海马区神经细胞自噬的协同作用
- Author:
Chaowang AN
1
;
Yao LIU
;
Xiaoyun ZHAO
;
Ying HAN
;
Yaning ZHAO
;
Xu ZHAO
;
Jianmin LI
;
Chengjing XUE
Author Information
1. 华北理工大学附属医院神经外科
- Keywords:
subarachnoid hemorrhage;
extracellular signal regulated kinase;
phosphatidylinositol 3 kinase;
autophagy
- From:
Journal of China Medical University
2017;46(11):995-1000
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate synergistic effects of extracellular signal regulated kinase (ERK1/2) and phosphatidylinositol 3 kinase (PI3-K) pathway inhibitors on autophagy in the hippocampus of rats with subarachnoid hemorrhage (SAH),for identification of therapeutic targets in SAH.Methods Totally,200 male SD rats were randomly divided into a sham operated group,SAH group,inhibitor U0126 group,inhibitor LY294002 group,and a U0126+ LY294002 group.Animal models were established by injecting autologous blood twice into the cisterna magna.Morphological changes in the hippocampus nerve cells were detected by HE staining;ERK1/2,PI3-K,beclin-1,and LC3 mRNA expression in the hippocampus were detected by real-time PCR,and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein expression were detected by immunohistochemistry.Results Neuronal death rate and phosphorylated ERK1/2,PI3-K,beclin-1,and LC3-Ⅱ levels in the hippocampus in the SAH group were higher than in the sham group (all P ＜ 0.05).Neuronal death rate in U0126 or LY294002 group was higher than in SAH group,while ERK1/2,PI3-K,beclin-1,and LC3 mRNA and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein levels were lower than in SAH group (all P ＜ 0.05).Neuronal death rate in U0126 +LY294002 group was higher than in U0126 or LY294002 group,while ERK1/2,PI3-K,beclin-1,LC3 mRNA and phosphorylated ERK 1/2,PI3-K,beclin-1,and LC3-Ⅱ protein levels in the hippocampus were lower than in U0126 or LY294002 group (all P ＜ 0.05).Conclusion Co-targeting the inhibition of ERK 1/2 and PI3-K pathways can significantly reduce neuronal cell autophagy and aggravate cells loss after SAH.
