大脑中动脉缺血再灌注大鼠脑组织PAR1表达与炎症反应的关系.docVIP

大脑中动脉缺血再灌注大鼠脑组织PAR1表达与炎症反应的关系 作者：周青珍， 王华梅， 吴家幂 【摘要】 目的: 研究 脑缺血再灌注（CIR）后脑组织中蛋白酶激活受体1(PAR1）的表达及其与炎症反应的关系。 方法 :40只雄性SD大鼠线栓法建立大脑中动脉栓塞（MCAO）模型，再灌注后于3 、6 、12 h及1 、2 、3 、7 d取脑，免疫组化法和脑组织匀浆法检测PAR1、超氧化物歧化酶（SOD）和丙二醛（MDA）的含量。 结果:缺血再灌注后脑组织PAR1表达增加（P＜0.01），MDA含量增多（P＜0.01），SOD活性降低（P＜0.01）；PAR1表达与MDA含量正相关（r1=0.844,P＜0.05），与SOD含量负相关（r2=-0.901,P＜0.01）。 结论:CIR后PAR1表达增多可加重脑组织炎性反应。 【关键词】 大脑中动脉;栓塞；蛋白酶激活受体1 Abstract: Objective To investigate the correlation between proteaseactivated receptor1(PAR1) expression and inflammatory reaction of brain tissue after cerebral ischemia reperfusion(CIR).Methods Fourty SD rats were randomly divided into Eight groups:sham group,CIR3 h,CIR6 h,CIR12 h,CIR1 d,CIR2 d, CIR3 d,and CIR7 d group(n=5).To establish middle cerebral artery occlusion(MCAO) model with Longa’ methods.At the indicated timepoint,the rat was sacrificed and its brain was removed.PAR1 was detected with immunohistochemistry,SOD and MDA contents in brain homogenate were measured.Results Compared with sham group,PAR1 expression was increased obviously（P＜0.01）.Contents of MDA were increased with the time of CIR prolonged（P＜0.01）,and there was positive correlation between PAR1 expression and MDA content（r1=0.844,P＜0.05）,but SOD activity was decreased（P＜0.01）,and negatively correlated with PAR1 expression（r2=-0.901,P＜0.01）. Conclusion Increased PAR1 expression may aggravate inflammatory reaction of brain tissue in rats after CIR with MCAO. Key words: Middle cerebral artery;Occlusion;Proteaseactivated receptor1 近年来研究发现中性粒细胞的聚集、黏附和浸润，以及炎性因子的大量产生是缺血再灌注损伤的重要因素[2]。脑缺血再灌注（cerebral ischemia reperfusion,CIR）后中性粒细胞在凝血酶作用下趋化于缺血组织周围，通过激活蛋白酶激活受体-1（proteaseactivated receptor1,PAR1）导致细胞内Ca2+升高，刺激小胶质细胞的活化和增生[3]，促进炎症因子表达，活化的白细胞释放自由基，引起脑缺血后脑组织损害。本实验通过建立大脑中动脉栓塞（Middle cerebral artery occlusion,MCAO）模型,了解CIR后脑组织中PAR1表达与代表自由基水平的超氧化物歧化酶（superoxide dismutase，SOD）和丙二醛（malondialdehyde，MDA）之间的相关性， 以探讨PAR1在CIR后脑组织炎症反应中的作用。 1 材料和方法 1.1 实验动物与分组 健康雄性SD大鼠40只，体重270～320 g(南京青龙山实验动物养殖中心提供），随机分为8组：假手术组