Role of ERK signaling pathway in inhibition of OGD/R-induced apoptosis in rat cortical neurons by sevoflurane: the relationship with mPTP
10.3760/cma.j.issn.0254-1416.2016.04.018
- VernacularTitle:ERK信号通路在七氟醚抑制大鼠氧糖剥夺-复糖复氧皮质神经元凋亡中的作用:与mPTP的关系
- Author:
Chunling WU
;
Limin ZHANG
;
Dongxue ZHANG
;
Wenbo SUN
;
Rui LI
;
Xingliao LUO
- Publication Type:Journal Article
- Keywords:
Extracellular signal-regulated MAP kinases;
Mitochondrial membrane transport proteins;
Anesthetics,inhalation;
Neurons;
Apoptosis
- From:
Chinese Journal of Anesthesiology
2016;36(4):452-455
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in inhibition of oxygen-glucose deprivation and restoration (OGD/R)-induced apoptosis in rat cortical neurons by sevoflurane and the relationship with mitochondrial permeability transition pore (mPTP).Methods The rat cortical neurons were cultured in vitro and seeded in 6-well or 12-well culture plates.The neurons were randomly divided into 4 groups (n =18 each) using a random number table:control group (group C);OGD/R group (group O);sevoflurane group (group OS);sevoflurane + ERK1/2 inhibitor PD98059 group (group OSP).The neurons were subjected to O2-glucose deprivation for 90 min followed by restoration of O2-glucose supply for 24 h in group O.The neurons were incubated with 2％ sevoflurane for 2 h after OGD/R in group OS.OGD/R was performed at 1 h after ERK1/2 inhibitor PD98059 30 μmol/L was added,and the neurons were incubated with 2％ sevoflurane for 2 h after OGD/R in group OSP.At 24 h of restoration of O2-glucose supply,the expression of phosphorylated ERK1/2 (p-ERK1/2) in neurons was measured by Western blot,the neuronal apoptosis was detected using Annexin V-FITC/PI double staining combined with flow cytometry,and the opening of mPTP was determined through measuring the optical density at 540 nm.The apoptosis rate was calculated.Results Compared with group C,the expression of p-ERK1/2 in neurons was significantly up-regulated,and the apoptosis rate and mPTP opening were significantly increased in group O (P＜0.05).Compared with group O,the expression of p-ERK1/2 in neurons was significantly up-regulated,and the apoptosis rate and mPTP opening were significantly decreased in group OS (P＜0.05).Compared with group OS,the expression of p-ERK1/2 in neurons was significantly down-regulated,and the apoptosis rate and mPTP opening were significantly increased in group OSP (P＜0.05).Conclusion The mechanism by which sevoflurane inhibits OGD/R-induced apoptosis in rat cortical neurons is related to inhibition of mPTP opening after activation of ERK signaling pathway.
