Inhibiting ERK1/2 pathway reduces brain edema and down-regulates matrix metalloproteinase-9 expression after subarachnoid hemorrhage in rats
10.3760/cma.j.issn.1673-4165.2011.02.008
- VernacularTitle:抑制ERK1/2可减轻蛛网膜下腔出血大鼠脑水肿和下调基质金属蛋白酶-9表达
- Author:
Jiyang AN
;
Haitao JIANG
;
Jie CHEN
;
Jiangtao XIE
- Publication Type:Journal Article
- Keywords:
Protein-serine-threonine kinases;
Mitogen-activated protein kinase 1;
Subarachnoid hemorrhage;
Blood-brain barrier;
Matrix metalloproteinase 9;
Disease models,animal;
Rats
- From:
International Journal of Cerebrovascular Diseases
2011;19(2):115-121
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of extracellular signal-regulated kinase1/2 (ERK1/2)inhibitor U0126 on matrix metalloproteinase-9(MMP-9)in brain tissue after subarachnoid hemorrhage(SAH)in rats and to investigate the action mechanisms of ERK1/2 and M M P-9 in blood-brain barrier(BBB)injury and brain edema after SAH.Methods Seventy-two male Sprague-Dawley rats were randomly divided into four groups:SAH model,sham operation,U0126 intervention,and vehicle groups.A SAH model was induced by injection of autologous blood into cisterna magna once.The dry-wet weight method was used to detected brain tissue water content in order to evaluate cerebral edema.BBB permeability was evaluated by the Evans blue extravasation method.The immunohistochemical method was used to detect the expression of MMP-9 and phosphorylated ERK1/2.Results The expression of phosphorylated ERK1/2 and MMP-9 was lower in the sham operation group.The expression of both was up regulated at 24 hours after SAH.The brain water content and Evans blue content also increased.U0126 treatment decreased the phosphorylation of ERK1/2 and the expression of MMP-9,improved the BBB permeability,and alleviated brain edema.Conclusions MMP-9 is involved in the pathophysiological processes of early BBB injury and brain edema aft er SAH.ERK1/2 pathway may play a vital role in the expression of MMP-9.U0126 may protect BBB and reduce brain edema after SAH by inhibiting the phosphorylation of ERK1/2.
