Notch-1/NICD信号在普罗布考保护大鼠急性脑缺血后再灌注损伤中的作用

Role of Notch-1/NICD signaling in probucol’s protection on rats with acute cerebral ischemia reperfusion injury and its mechanism

目的：研究普罗布考对大鼠急性脑缺血再灌注损伤后大脑的保护作用及其与Notch-1/Notch胞内域（NICD）蛋白信号通路的关系。方法：SD大鼠随机分为假手术组、缺血组及普罗布考组。采用大脑中动脉闭塞（MCAO）法建立局灶性脑缺血再灌注模型，经普罗布考腹腔注射处理后，采用转角试验判断神经功能，2,3,5氯化三苯四氮唑（TTC）染色法测量脑梗死体积，干湿法测定脑组织含水量，免疫印迹检测Notch-1和NICD蛋白的表达，免疫酶联反应检测血清中炎症因子白介素8（IL-8）和肿瘤坏死因子-α（TNF-α）的含量。结果：普罗布考可改善急性脑缺血再灌注损伤大鼠的神经功能，减轻脑水肿；与缺血组相比，普罗布考治疗组Notch-1/NICD蛋白表达降低，IL-8和TNF-α分泌也相应减少。结论：普罗布考可激活Notch-1/NICD信号通路，进而调节IL-8和TNF-α的表达，发挥对急性脑缺血再灌注损伤脑的保护作用。

Objective： To study the role and mechanism of probucol in protecting the brain of rats with acute cerebral ischemia reperfusion injury and its relationship with Notch-1 signaling pathway, Methods, SD rats were randomly divided into sham operation group, ischemia group and probucol group. Middle cerebral artery occlusion（MCAO） of rats were treated with probucol. The neurological score was observed v/a corner turn test. The volume fraction of infarct tissue was assessed by 2, 3,5-triphenyltetrazolium chloride（TTC） dyeing method. The brain water content was measured by dry-wet weight method. The expressions of Notch-1 and intracellular domain of Notch （NICD） were detected by Western blotting. The serum level of interleukin-8 （IL-8） and tumor necrosis factor-α （TNF-a） were detected by enzyme-linked immunosorbent assay （ELISA）. Results ： Probucol improved the neurological deficits and decreased brain water content. The expressions of Notch-1 and NICD and the secretion of IL-8 and TNF-a in probucol group were significantly decreased compared with ischemia group. Conclusion： Prohucol can activate Notch-1/NICD signaling pathways, which regulates the expression of IL-8 and TNF-a and plays a role in brain protection with acute cerebral ischemia reper/usion injury.