氟比洛芬酯后处理对大鼠局灶性脑缺血再灌注时血脑屏障通透性的影响  

Effect of flurbiprofen postconditioning on permeability of blood brain barrier in a rat model of focal cerebral ischemia-reperfusion injury

作　　者：侯莉莉 陈琳 杨晓玫[3] 魏欣冰 张岫美 孙宝柱[3] Hou Lili;Chen Lin;Yang Xiaomei;Wei Xinbing;Zhang Xiumei;Sun Baozhu(Department of Health Management Center,the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250012,China;Institute of Pharmacology,Cheeleoo College of Medicine,Shandong University,Jinan 250012,China;Department of Anesthesiology,Qilu Hospital,Cheeleoo College of Medicine,Shandong University,Jinan 250012,China)

机构地区：[1]山东省中医药大学第二附属医院健康体检中心,250012 [2]山东大学齐鲁医学院药理研究所,250012 [3]山东大学齐鲁医院麻醉科,250012

出　　处：《中华麻醉学杂志》2020年第7期813-816,共4页Chinese Journal of Anesthesiology

基　　金：山东省自然科学基金(ZR2010HM082)。

摘　　要：目的评价氟比洛芬酯后处理对局灶性脑缺血再灌注大鼠血脑屏障通透性的影响。方法健康雄性Wistar大鼠80只,8~9周龄,体重280~320 g,采用随机数字表法分为4组(n=20):假手术组(Sham组)、脑缺血再灌注组(I/R组)、脂微球溶剂组(V组)和氟比洛芬酯10 mg/kg后处理组(F组)。采用改良线栓法制备大鼠局灶性脑缺血再灌注损伤模型。再灌注即刻F组尾静脉注射氟比洛芬酯10 mg/kg,V组尾静脉注射等容量脂微球,S组和I/R组尾静脉注射等容量生理盐水。再灌注24 h时处死大鼠,取脑组织测定水含量和伊文思蓝(EB)含量;采用免疫组化法检测缺血区脑组织基质金属蛋白酶9(MMP-9)表达;采用Western blot法检测缺血区脑组织磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)和诱导型一氧化氮合酶(iNOS)的表达。结果与Sham组比较,I/R组、V组和F组脑组织EB含量和水含量均升高,缺血区脑组织MMP-9、p-p38 MAPK和iNOS表达上调(P<0.05);与I/R组比较,F组脑组织EB含量和水含量降低,缺血区脑组织MMP-9、p-p38 MAPK和iNOS表达下调(P<0.05),V组上述各指标差异无统计学意义(P>0.05)。结论氟比洛芬酯后处理可降低大鼠脑缺血再灌注时血脑屏障通透性,其机制可能与抑制p38 MAPK/iNOS信号通路激活,下调MMP-9的表达有关。Objective To evaluate the effect of flurbiprofen postconditioning on the permeability of blood brain barrier in a rat model of focal cerebral ischemia-reperfusion(I/R)injury.Methods Eighty healthy male Wistar rats,aged 8-9 weeks,weighing 280-320 g,were divided into 4 groups(n=20 each)using a random number table method:sham operation group(group Sham),focal cerebral I/R group(group I/R),lipo-microballoons group(group V)and flurbiprofen 10 mg/kg group(group F).Focal cerebral I/R model was established by left middle cerebral artery occlusion for 2 h followed by 24-h reperfusion in anesthetized rats.Flurbiprofen 10 mg/kg(group F),the equal volume of lipo-microballoons(group V)or the equal volume of normal saline(group Sham and group I/R)was injected via the tail vein at the onset of reperfusion.The rats were sacrificed at 24 h of reperfusion,brains were immediately removed,and cerebral tissues were obtained for measurement of brain water content,Evans blue content,expression of matrix metalloproteinase-9(MMP-9)in ischemic penumbra(by immuno-histochemistry),and expression of phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)and inducible nitric oxide synthase(iNOS)in ischemic penumbra(by Western blot).Results Compared with Sham group,brain water content and Evans blue content in brain tissues were significantly increased,and the expression of MMP-9,p-p38 MAPK and iNOS in ischemic penumbra was up-regulated in I/R,V and F groups(P<0.05).Compared with group I/R,brain water content and Evans blue content in brain tissues were significantly decreased,and the expression of MMP-9,p-p38 MAPK and iNOS in ischemic penumbra was down-regulated in group F(P<0.05),and no significant change was found in the above parameters in group V(P>0.05).Conclusion Flurbiprofen postconditioning can decrease the permeability of blood brain barrier during focal cerebral I/R in rats,and the mechanism may be related to inhibiting the activation of p38 MAPK/iNOS signaling pathway and down-regulating the expression of MMP-9.

关 键 词：氟比洛芬 缺血后处理 脑 再灌注损伤 血脑屏障 

分 类 号：R743.3[医药卫生—神经病学与精神病学]