Role of AMP-activated protein kinase signal path in cell autophagy activation at early brain injury in rats after subarachnoid hemorrhage
10.3760/cma.j.issn.1671-8925.2015.11.003
- VernacularTitle:AMPK信号通路在蛛网膜下腔出血后自噬激活中的作用及机制
- Author:
Jiyang AN
1
;
Lili ZHOU
;
Honggang PANG
;
Xianhua LUO
;
Peng SUN
;
Jinning SONG
Author Information
1. 西安交通大学医学院第一附属医院神经外科
- Keywords:
Subarachnoid hemorrhage;
Early brain injury;
AMP-activated protein kinase;
Autophagy;
Mammalian target of rapamycin
- From:
Chinese Journal of Neuromedicine
2015;14(11):1095-1099
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of AMP-activated protein kinase (AMPK) signal path in cell autophagy activation at early brain injury in rats after subarachnoid hemorrhage (SAH).Methods Adult male SD rats (weighting 300-350 g) were divided into five groups (n=12):sham-operated group,SAH group,and SAH+AICAR group,SAH+Compound C group and SAH+vehicle group.SAH models in the later four groups were established by endovascular perforation technique,and rats in the later three groups were performed left intracerebroventricular injection of AMPK agonist AICAR,AMPK inhibitor Compound C or normal saline 30 min before modeling;animals were subsequently sacrificed at 24 h after modeling.Immunohistochemical method was used to detect the phosphorylated mammalian target of rapamycin (p-mTOR) expression.Expressions of cortex autophagy related proteins LC3,AMPK and phosphorylated AMPK (p-AMPK) were observed by Western blotting.Loeffler's method was used to evaluate the neurologic behavior scores.Results As compared with those in the sham-operated group,the p-AMPK level,p-mTOR expression level and LC3Ⅱ/LC3Ⅰ ratio were significantly increased,while the behavioral deficit scores were significantly lower in the SAH group,with statistical differences (P＜0.05);the p-mTOR mainly expressed at cortex surrounding the hemorrhage areas,and integration areas of deep cortex and brain white matter.As compared with the sham-operated group and SAH+vehicle group,SAH+AICAR group had significantly increased p-AMPK level,decreased p-mTOR expression level,increased LC3Ⅱ/LC3Ⅰ ratio,and decreased behavioral deficit scores (P＜0.05);as compared with the sham-operated group and SAH+vehicle group,SAH+Compound C group had significantly decreased p-AMPK level,decreased LC3Ⅱ/LC3Ⅰ ratio,and decreased behavioral deficit scores (P＜0.05).Conclusion AMPK is involved in the process ofautophagy activation after SAH through regulating mTOR,and the regulation of AMPK may contribute to neuroprotection related to autophagy.
