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远隔缺血后适应通过水通道蛋白-4对局灶性脑缺血再灌注大鼠的血脑屏障保护机制

Blood-brain barrier protection mechanism in rats undergoing focal cerebral ischemia and reperfusion via aquaporin-4
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摘要 目的:研究远隔缺血后适应对大鼠局灶性脑缺血再灌注后脑组织内水通道蛋白-4(AQP4)的表达及对血脑屏障通透性的影响。方法:采用线栓法建立大脑中动脉栓塞再灌注(MCAO/R)模型。将75只雄性SD大鼠随机平均分为3组:假手术组(Sham组)、再灌注组(I/R组)、后适应组(RIPC组)。再灌注24h后对每组大鼠进行:神经功能评分,脑组织含水量,海马区神经元形态及病理损伤变化,脑梗死体积,评估血脑屏障的通透性,水通道蛋白-4的表达。结果:与Sham组相比,I/R组的大鼠表现出明显神经功能障碍,脑组织水肿明显,苏木素-伊红(HE)染色缺血侧海马CA1区呈现出明显的病理性改变,脑组织缺血侧呈白色,梗死范围较大,伊文氏蓝含量显著升高,AQP4的表达明显升高。RIPC组的大鼠比I/R组有明显改善,但差于Sham组。结论:远隔缺血后适应对大鼠脑缺血再灌注血脑屏障损伤有保护作用,可能通过下调AQP4的表达,降低血脑屏障的通透性有关。下肢作为远隔缺血后适应的器官是安全可行的,值得临床上进一步探讨。 Objective:The study investigated the effect of remote ischemic post-conditioning on the expression of aquaporin-4(AQP4)and blood-brain barrier permeability in rats with focal cerebral ischemia/reperfusion injury.Methods:Middle cerebral artery embolization reperfusion(MCAO/R)model was established by line bolt method.The 75 male SD rats were randomly divided into 3 groups:sham group(Sham group),ischemia reperfusion group(I/R group),and distant ischemic postconditioning group(RIPC group).Neurofunction was scored for each group 24h after reperfusion,brain water content,neuronal morphology and pathological damage changes in the hippocampus,rat cerebral infarction volume,assessment of BBB permeability,and aquaporin-4 expression.Results:Compared with the sham group,rats in the I/R group showed significant neurological dysfunction,significant edema,significant pathological changes in CA1 hippocampus of hematoxylin-eosin(HE)staining,white ischemic side,large infarction,increased evin blue,and increased expression of AQP 4.Rats in the RIPC group showed significant improvement over the I/R group but worse than the sham group.Conclusion:The adaptation after distant ischemia has a protective effect on BBB injury in rats,which may be related to the reduction of BBB permeability by downregulating AQP 4 expression.The lower limb as an organ adapted after distant interval ischemia is safe and feasible and deserves further clinical exploration.
作者 杨军 安贵良 刘子琨 李浩然 宋广福 YANG Jun;AN Gui-liang;LIU Zi-kun;LI Hao-ran;SONG Guang-fu(Department of Neurosurgery of the First Affiliated Hospital of Jiamusi University,Jiamusi 154003,China)
出处 《黑龙江医药科学》 2023年第5期27-30,共4页 Heilongjiang Medicine and Pharmacy
基金 黑龙江省卫生健康委科研课题,编号:20210404040046。
关键词 远隔缺血后适应 缺血再灌注 水通道蛋白-4 血脑屏障 脑水肿 remote ischemic post-conditioning ischemia-reperfusion AQP4 blood-brain barrier brain edema
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