Protective effect and possible mechanism of Exendin-4 on apoptosis of rat cortical neuron induced by in vitro ischemia/reperfusion
10.3760/cma.j.issn.1006-7876.2011.04.005
- VernacularTitle:Exendin-4抑制缺血再灌注损伤大鼠皮质神经元凋亡及可能机制
- Author:
Mengdie WANG
;
Junmin LI
;
Yuan FANG
;
Yuanwu MEI
- Publication Type:Journal Article
- Keywords:
Reperfusion Injury;
Cerebral cortex;
Neurons;
Apoptosis;
Peptides;
Venoms;
Rats
- From:
Chinese Journal of Neurology
2011;44(4):242-246
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Exendin-4 (Ex-4) on ischemia/reperfusion (I/R) injury-induced apoptosis in primary rat cortical neurons and the possible underlying mechanisms.Methods Rat cortical neurons were cultured in vitro,identified by NES-immunohistological staining and immunofluorescence staining,and randomly divided into the following groups: control group,I/R group and Ex-4 group.RT-PCR was performed to establish the existence of active glucagon-like peptide-1 receptor (GLP-1R).ELISA was used to measure the neuronal cytoplasmic cAMP level. MTT was used to detect viability. Fluorescent DNA binding dye Hoechest 33258 was used to reveal apoptosis. C/EBP-homologous protein (CHOP) and growth arrest and DNA-damage-inducible gene 34 (GADD34) mRNAs were detected by real-time PCR. Results The apoptosis rate induced by ischemia 6 h/reperfusion 12 h was 77.0% ±5.3% and was decreased to 27.0% ± 3.5% after Ex-4 ( 0. 4 μg/ml ) treating ( t = 19. 462,P ＜ 0. 01 ).Levels of CHOP and GADD34 mRNA in cortical neurons increased since 4 h and peaked at 12 h after reperfusion. Ex-4 group showed a sharp elevation of levels of CHOP and GADD34 mRNA,peaking at 8 h reperfusion,and then tended to decrease.Conclusions Ex-4 has protective effect against rat cortical neurons injury induced by ischemia/reperfusion. The protective effect may be related to inhibition of ESR-related neuron apoptosis via regulation of unfolded protein response.
