Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury.
10.4062/biomolther.2015.206
- Author:
Kun WANG
1
;
Xiangang KONG
Author Information
1. Department of Anesthesiology, Jining No.1 People's Hospital, Jining, Shandong 272011, China. kongxiangang4418@126.com
- Publication Type:Original Article
- Keywords:
Isoflurane;
Spinal cord ischemic injury;
TREK1;
Caspase-3;
NADH
- MeSH:
Adult;
Animals;
Blotting, Western;
Caspase 3;
Cell Cycle;
Humans;
Ischemia;
Isoflurane*;
Male;
Models, Animal*;
NAD;
Neurons;
Neuroprotection*;
Rats*;
Rats, Sprague-Dawley;
RNA, Messenger;
Spinal Cord*;
Up-Regulation*
- From:Biomolecules & Therapeutics
2016;24(5):495-500
- CountryRepublic of Korea
- Language:English
-
Abstract:
This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related K⁺ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1.
