实验性蛛网膜下腔出血核因子E2相关因子2-抗氧化反应原件通路的表达  

Expression of nuclear factor-E2-related factor 2-antioxidant response element pathway in experimental subarachnoid hemorrhage

作　　者：吴琪[1] 赵旭东[2] 王汉东[1] 张鑫[1] 

机构地区：[1]南京军区南京总医院神经外科 [2]无锡市第二人民医院神经外科

出　　处：《医学研究生学报》2012年第11期1132-1135,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81070974)

摘　　要：目的脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后严重的并发症,机制仍不明确。文中研究SAH后血管中核因子E2相关因子2-抗氧化反应原件(nuclear factor-E2-related factor 2-antioxi-dant response elements,Nrf2-ARE)通路的表达及与CVS的关系。方法将48只新西兰兔随机分为:对照组、SAH后3 d组,SAH后5 d组和SAH后7 d组;将以上各组再随机分为2组,分别用于组织学及分子生物学检验,每组6只。枕大池2次注血法建立兔SAH模型,留取基底动脉标本。检测Nrf2 mRNA水平与蛋白水平的表达,并测定血管组织中谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)的活力。脑血管痉挛的程度通过测定基底动脉血管横截面积来判断。结果基底动脉于SAH后发生血管痉挛,并于SAH后3 d及5 d组更为严重。SAH组Nrf2 mRNA的表达显著增加(P<0.05),且表达无时效相关性。SAH组Nrf2蛋白的表达显著增加(P<0.05),并于第3天、第5天达到高峰。SAH后GPx的活力下降(P<0.05),于第3天、第5天降至最低。Nrf2 Western blot结果与基底动脉横截面积呈负相关(r=-0.791,P<0.05);GPx活力与基底动脉横截面积呈正相关(r=0.906,P<0.05)。结论 SAH的动物模型中,Nrf2于SAH后的基底动脉中表达上升,提示其表达可能在SAH后发生CVS的病理生理机制中发挥作用,但其具体作用有待进一步研究。Objective Cerebral vasospasm（CVS） is a severe complication after subarachnoid hemorrhage（SAH）,but its pathophysiologic mechanism is not clear.The aim of this article is to study the expression of nuclear factor-E2-related factor 2-antioxidant（Nrf2-ARE） pathway in the artery after SAH and its relationship with CVS.Methods Forty-eight New Zealand rabbits were randomly assigned to four groups（control,3 d post-SAH,5 d post-SAH and 7 d post-SAH）,each again divided into two subgroups（n=6） for histological and molecular biological examination,respectively.Rabbit SAH models were constructed by double injection of blood into the occipital cistern,with the basilar arteries of entire length reserved.The mRNA and protein expressions of Nrf2 were detected by RT-PCR and Western blot,respectively,the activity of Glutathione peroxidase（GPx） in the arteries were determined,and level of CVS measured by assessing the cross-sectional area of the basilar artery.Results The basilar arteries exhibited vasospasm after SAH,even more severe 3 d and 5 d post-SAH groups.The expression of Nrf2 mRNA was increased significantly after SAH（P0.05）,but not in a time-dependent manner,and so was that of Nrf2 protein（P0.05）,which peaked at 3 and 5 days.The activity of Gpx was markedly decreased after SAH（P0.05）,to the lowest level at 3 and 5 days.The cross-sectional area of the basilar artery was correlated negatively with Nrf2（r=-0.791,P0.05）,but positively with the activity of GPx（r=0.906,P0.05）.Conclusion The elevated expression of Nrf2 in the basilar artery of the rabbit SAH model suggested a role of Nrf2 in the pathophysiologic mechanism of CVS after SAH,though it deserves further studies.

关 键 词：蛛网膜下腔出血 脑血管痉挛 核因子E2相关因子 氧化应激 

分 类 号：R743.35[医药卫生—神经病学与精神病学]