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

摘要

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.%目的：研究5-脂氧合酶(5-lipoxygenase,5-LOX)抑制剂齐留通( zileuton)是否通过激活ERK1/2信号通路减轻大鼠脑缺血诱导的炎症反应和缺血性脑损伤。方法制备大鼠脑缺血模型,随机分为对照组、溶媒组、zileuton治疗组和PD98059干预组, zileuton (50 mg · kg-1)经口服给药, PD98059经脑室内给药。对大鼠神经功能损伤进行评分,测量大鼠脑梗死体积；分析大鼠缺血性脑水肿程度；检测脑组织髓过氧物酶的含量；Western blot法检测信号通路关键蛋白p-ERK1/2、t-ERK1/2的表达变化；ELISA 法检测血浆TNF-α的分泌。结果 Zileuton治疗组能明显减轻大鼠神经功能障碍、脑梗死体积、脑水肿、MPO活性及TNF-α含量,且zileuton的这种脑保护作用和抗炎症作用被PD98059抑制。Zileuton可上调p-ERK1/2的表达,同时也被PD98059抑制。结论5-LOX抑制剂zileuton通过激活ERK1/2信号通路,减轻脑缺血诱导的炎症反应和缺血性脑损伤。