Protective role of inhibition of adenosine monophosphate activated protein kinase activity in cerebral ischemia-induced blood brain barrier injury and its mechanism
10.3760/cma.j.issn.1671-8925.2015.09.010
- VernacularTitle:抑制腺苷酸活化蛋白激酶活性对MCAO大鼠血脑屏障的保护作用及机制研究
- Author:
Rui LI
1
;
Li ZHANG
;
Yanbing YU
;
Sixun ZHANG
;
Yue YUAN
;
Jia YOU
;
Qing FANG
Author Information
1. 中日友好医院临床医学研究所
- Keywords:
AMP-activated protein kinase;
Ischemia/reperfusion;
Blood brain barrier;
Matrix metalloproteinase
- From:
Chinese Journal of Neuromedicine
2015;14(9):910-917
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on blood brain barrier (BBB) and its mechanism in hypoxic/ischemic models.Methods Two hundred healthy male SD rats were randomly divided into sham-operated group,model group (ischemia 2 h-reperfusion 0,24 and 72 h [I/R]),and Compound C treated group (giving intraperitoneal injection of 20 mg/kg AMPK specific inhibitor Compound C).Focal cerebral ischemia rat models were established by occluding the middle cerebral artery (MCAO).Neurological deficit was determined by Zea Longa test,infarct size and brain water content were measured by TTC staining,leakage of BBB was determined by Evans blue (EB) staining.Expressions of matrix metalloproteinase (MMP)-2/MMP-9 and nuclear factor (NF)-κB,and release of inflammatory factors were detected by Western blotting.Results As compared with those in the model group,significantly reduced neurological deficit scores in Compound C treated group were noted at I/R 0,24 and 72 h (P＜0.05).After I/R 72 h,Compound C treated group had significantly reduced brain infarct size,brain water content and EB leakage as compared with model group (P＜0.05).The expressions of MMP2/MMP9 in model group (52.58±8.12 and 33.15±6.45) were significantly higher than those in the Compound C treated group (21.20±3.39 and 15.46±4.71,P＜0.05).What is more,as compared with the model group,Compound C treated group had significantly reduced expressions of NF-κB and inflammatory factors (P＜0.05).Conclusions Inhibition of AMPK shows a protective role in BBB after ischemic injury,mainly by inhibiting NF-κB signaling pathway,inhibiting the expression of MMP-2/MMP-9 to reduce the degradation of the base metal film,and maintain the integrity of BBB,thus,improving the ischemic symptoms,reducing the brain water content and reducing infarct size.
