5-lipoxygenase inhibitor zileuton attenuates neuroinflammation and brain damage via modulating ERK1/2 signaling pathway in rats of cerebral ischemia
10.3969/j.issn.1001-1978.2014.10.023
- VernacularTitle:齐留通通过激活ERK1/2信号通路减轻大鼠脑缺血炎症反应和缺血性脑损伤
- Author:
Xiankun TU
;
Songsheng SHI
;
Weizhong YANG
;
Jianping CHEN
;
Yan CHEN
;
Lisheng WANG
- Publication Type:Journal Article
- Keywords:
5-lipoxygenase;
cerebral ischemia;
inflam-mation;
zileuton;
ERK1/2;
TNF-α
- From:
Chinese Pharmacological Bulletin
2014;(10):1441-1444
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore whether 5-lipoxygenase inhibitor zileuton attenuates neuroinflammation and brain damage via modulating ERK1/2 signaling path-way in rats of cerebral ischemia, and further investigate the possible mechanisms. Methods Sprague-Dawley rats underwent the cerebral ischemic injury by the su-ture occlusion model, and were randomly divided into sham operation, MCAO, zileuton-treated and PD98059 groups. Neurological deficit scores, cerebral infarct volume, and cerebral water content were measured, myeloperoxidase ( MPO ) activities in rat brain were measured as an index of neutrophil infiltration;content of TNF-α in blood was determined by the method of ELISA;expression of p-ERK1/2 and t-ERK1/2 in rat brain were detected by Western blot. Results Zileu-ton reduced neurological deficit scores, cerebral infarct volume, cerebral water content, MPO activity and TNF-α content, all of which were abolished by PD98059 administration. Zileuton up-regulated the ex-pression of p-ERK1/2 , which was inhibited by PD98059 administration. Conclusions Zileuton at-tenuates neuroinflammation and ischemic brain damage through the activation of ERK1/2 signaling pathway.
