Effects of adenosine 5’monophosphate-activated protein kinase on europrotection induced by ischemic preconditioning
10.11855/j.issn.0577-7402.2015.05.07
- Author:
Yuan-Ru-Hua TIAN
1
Author Information
1. Department of Neurology, General Hospital of Shenyang Command
- Publication Type:Journal Article
- Keywords:
Amp-activated protein kinases;
Brain ischemia;
Compound C;
Infarction;
Metformin;
Middle cerebral artery
- From:
Medical Journal of Chinese People's Liberation Army
2015;40(5):366-371
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of adenosine 5'-monophosphate-activated protein kinase (AMPK) and phosphated AMPK (pAMPK) signals in ischemic preconditioning (IPC), and the effect of pharmacological intervention of AMPK on infarct size of the brain. Methods A brief (3min) middle cerebral artery occlusion (MCAO) was employed to induce IPC in male rat, and another 90-min MCAO was performed 4 or 72h later. The levels of AMPK and pAMPK were assessed after IPC. A pharmacological activator metformin, or inhibitor compound C of AMPK, was used to analyze the correlation of IPC to AMPK signaling in MCAO rats. Results The infarct size of total cerebral hemisphere and cortex was significantly decreased in MCAO animals by IPC for 72h (P<0.05, n=8), and the neurological deficit scores (NDS) of MCAO rats were also improved (P<0.05, n=8). There was a significant increase in pAMPK expression after a 90min MCAO (P<0.05, n=6), and a significant decrease in induced pAMPK expression (P<0.05, n=6) achieved only by a 72h IPC treatment. Intraperitoneal injection of an AMPK inhibitor, compound C, could decrease the infarct size in MCAO rats (P<0.05, n=6), but combined IPC (72h) and injection of compound C did not result in further decrease of the infarct size (P>0.05, n=6). The AMPK activator metformin can significantly reverse the protective effect of IPC (P<0.05, n=6). Conclusions The signals of AMPK and pAMPK play an important role in neuroprotective effect of IPC on cerebral ischemic injury. The neuroprotective effect of IPC may be associated with the down-regulation of pAMPK.
