Protective effect of dexmedetomidine against glutamate-induced cytotoxicity in PC12 cells and its mechanism
10.3969/j.issn.1673-4254.2017.02.02
- VernacularTitle:右美托咪定对谷氨酸所致PC12细胞损伤的保护作用及其机制
- Author:
Weidong ZHANG
1
;
Hao ZHANG
;
Hai WANG
;
Na ZHANG
;
Chunyan DU
;
Jun YU
;
Zeguo FENG
Author Information
1. 解放军总医院麻醉手术中心
- Keywords:
dexmedetomidine;
PC12 cells;
glutamate
- From:
Journal of Southern Medical University
2017;37(2):150-156
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism.Methods PC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate.The cell viability was measured by MTT assay,and LDH release,MDA content and SOD activity were measured.The level of ROS was tested by DCFH-DA staining and flow cytometry.The level of intracellular Ca2+ was detected by Fluo-8 staining and flow cytometry,and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry.Results Within the concentration range of 0.01 to 100 μrnol/L,Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity.Treatment with 100 μmol/L Dex significantly increased the cell viability to (86.6±2.2)% of that of the control cells (P<0.01) and decreased LDH release to 1.4±0.1 folds of the control level (P<0.01).In PC12 cells exposed to glutamate,Dex pretreatment significantly reduced MDA content (P<0.01),enhanced SOD activity (P<0.01),inhibited ROS overproduction (P<0.01),reduced intracellular Ca2 + level (P<0.01) and maintained a stable MMP (P<0.01).Conclusion Dexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity,inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.