乌司他丁对小鼠脑缺血-再灌注损伤的保护作用及对Nrf2/HO-1通路影响的研究  

Ulinastatin activated Nrf2/HO-1 pathway and protected brain against ischemia/reperfusion injury

作　　者：李盼[1] 苏立凯[1] 李晓芳[1] 张祥建[2] 

机构地区：[1]河北大学附属医院神经内科,河北071000 [2]河北医科大学第二医院神经内科,河北省神经病学重点实验室

出　　处：《脑与神经疾病杂志》2015年第3期172-176,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金(81371287)

摘　　要：目的观察乌司他丁对小鼠脑缺血-再灌注后脑损伤的保护作用及对Nrf2/HO-1通路的影响。方法健康成年雄性CD1小鼠120只,随机分成4组(n=30):假手术组、脑缺血-再灌注组、乌司他丁小剂量组和乌司他丁大剂量组,采用改良线栓法制备大脑中动脉缺血-再灌注模型。缺血60min,再灌注24h后,采用Western blot和RT-q PCR来观察脑缺血后梗死侧皮质Nrf2和HO-1蛋白及基因表达变化,比较各组神经功能,脑梗死体积,脑组织含水量,梗死侧皮质丙二醛(MDA)和超氧化物歧化酶(SOD)含量。结果乌司他丁能够明显上调缺血脑皮质组织Nrf2、HO-1的表达,增加SOD活性,减少MDA的含量,改善神经功能缺失,减轻脑水肿,减小梗死体积。结论 Nrf2/HO-1通路参与了脑梗死后乌司他丁对缺血脑组织的保护作用。ObjectiveToinvestigatetheprotectiveeffectofulinastatinincerebralischemia-reperfusion injury and explore the influence of ulinastatin on the Nrf 2/HO-1 pathway in ischemic brain after focal cerebral ischemia.Methods Adult male CD1 mice were subjected to transient middle cerebral artery occlusion （ tMCAO） surgery .120 mice were divided into four groups randomly：Sham-operated group , vehicle group , low dose group , and high dose group .Neurological deficit scores , brain water content , infarct volume were measured at 24 h after reperfusion.Western blot and RT-qPCR were used to analyze the expressions of Nrf 2 and HO-1 in ischemic brain cortex, SOD and MDA were measured by spectrophotometer .Results Ulinastatin significantly up-regulated the expression of Nrf2 and HO-1, activated the antioxidant enzymes SOD and down-regulaed the formation of lipid＆amp;nbsp;peroxidative product MDA , ameliorated neurological deficits , brain edema and infarct volume .Conclusion Ulinastatin protected the brain from ischemic damage which maybe through the activation of the Nrf 2/HO-1 pathway .

关 键 词：脑缺血 NF-E2相关因子2 血红素氧合酶1 乌司他丁 

分 类 号：R743.3[医药卫生—神经病学与精神病学]