Sirt2抑制剂对大鼠出血性脑损伤的改善作用及其对血脑屏障通透性的影响  

Effects of Sirt2 Inhibitor on Hemorrhagic Brain Injury and Blood Brain Barrier Permeability in Rats

作　　者：吴亚芳 亢崇仰 陈悦华 陆兆丰 WU Yafang;KANG Chongyang;CHEN Yuehua;LU Zhaofeng(School of Clinical Medicine,Henan University of Science and Technology/First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471000,Henan,China)

机构地区：[1]河南科技大学临床医学院/河南科技大学第一附属医院,河南洛阳471000

出　　处：《中西医结合心脑血管病杂志》2022年第14期2545-2549,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：河南省科技发展计划项目(No.192102310081)。

摘　　要：目的探讨沉默信息调节因子2(Sirt2)抑制剂对大鼠出血性脑损伤的改善作用及对血脑屏障通透性的影响。方法45只健康SD大鼠,取15只作为假手术组,其余30只大鼠建模成功24只,将24只出血性脑损伤模型大鼠随机分为模型组与Sirt2抑制剂组,每组12只。Sirt2抑制剂组以25 mg/kg体质量Sirt2抑制剂腹腔注射,假手术组、模型组以等体积生理盐水腹腔注射。采用神经功能缺陷评分(NSS)评估神经功能损伤程度;酶联免疫吸附实验(ELISA)检测白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;干湿法测定脑组织湿重/干重(W/D)值;苏木精-伊红(HE)染色法检测脑组织病理形态学;伊文思蓝灌注染色法检测血脑屏障通透性;蛋白质印迹法检测Sirt2、核转录因子-κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)蛋白相对表达量。结果与模型组比较,Sirt2抑制剂组NSS评分降低(P<0.05);与假手术组比较,模型组、Sirt2抑制剂组IL-6、TNF-α水平及W/D值升高,且Sirt2抑制剂组低于模型组(P<0.05);HE染色显示,与模型组比较,Sirt2抑制剂组脑组织结构紊乱、局部出血、水肿、炎性细胞浸润等现象明显改善;与假手术组比较,模型组、Sirt2抑制剂组大脑皮层、基底节区伊文思蓝含量及Sirt2、p-NF-κB p65蛋白相对表达量升高,且Sirt2抑制剂组低于模型组(P<0.05)。结论Sirt2抑制剂可改善出血性脑损伤大鼠神经功能,减轻炎症反应、脑水肿,降低血脑屏障通透性,控制脑组织损伤,作用机制可能与抑制Sirt2/NF-κB通路有关。Objective To investigate the effect of silent information regulator 2(Sirt2)inhibitor on hemorrhagic brain injury and blood-brain barrier permeability in rats.Methods Forty-five healthy SD rats were selected,and 15 rats were randomly recruited as the shame operation group,of the other 30 rats,24 were successfully modeled and randomly divided into model group and Sirt2 inhibitor group,with 12 rats in each group.The rats in Sirt2 inhibitor group were intraperitoneally injected with 25 mg/kg Sirt2 inhibitor,and the rats in sham operation group and model group were intraperitoneally injected with equal volume of normal saline.The neurological deficit score(NSS)was used to evaluate the neurological impairment.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The wet weight/dry weight(W/D)of brain tissue was measured by dry wet method.Hematoxylin eosin(HE)staining was used to detect the pathological morphology of brain tissue.Blood brain barrier permeability was detected by Evans blue perfusion staining.Western Blot was used to detect the relative expression of Sirt2,NF-κB p65,and phosphorylated NF-κB p65(p-NF-κB p65).Results Compared with model group,the NSS score of Sirt2 inhibitor group was decreased(P<0.05).Compared with sham operation group,the levels of IL-6,TNF-α,and W/D in model group and Sirt2 inhibitor group were increased,and the levels of IL-6,TNF-α,and W/D in Sirt2 inhibitor group were lower than those in model group(P<0.05).HE staining showed that compared with model group,the disorder of brain tissue structure,local hemorrhage,edema,and inflammatory cell infiltration were significantly improved in Sirt2 inhibitor group.Compared with sham operation group,the content of Evans blue and the relative expression of Sirt2 and p-NF-κB p65 protein in cerebral cortex and basal ganglia in model group and Sirt2 inhibitor group were increased,and the levels of that in Sirt2 inhibitor group were lower than those in model group(P<0.05).C

关 键 词：出血性脑损伤 沉默信息调节因子2抑制剂 血脑屏障通透性 实验研究 

分 类 号：R651.15[医药卫生—外科学]