常压高浓度氧对脑缺血-再灌注大鼠缺血核心区核转录因子-κB的适度调节作用  

Moderate regulatory effect of normobaric hyperoxia on nuclear factor-κB in cerebral ischemia-reperfusion injured rats

作　　者：师文娟 赵咏梅 戚智锋 黄语悠 房亚兰 刘克建 Shi Wenjuan;Zhao Yongmei;Qi Zhifeng;Huang Yuyou;Fang Yalan;Liu Kejian(Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical Research Center,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing 100053, China)

机构地区：[1]首都医科大学宣武医院北京市老年病医疗研究中心脑血管病转化医学北京市重点实验室,北京100053

出　　处：《首都医科大学学报》2018年第3期349-354,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(81620108011;81571175)~~

摘　　要：目的探究常压高浓度氧治疗(normobaric hyperoxia,NBO)对脑缺血-再灌注大鼠脑内白细胞介素-1β(interleukin 1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、核转录因子(nuclear factor-κB,NF-κB)及其抑制蛋白(inhibitor ofκB,IκB)表达的影响,探讨NBO治疗对脑缺血后NF-κB介导的炎性反应损伤的作用。方法将15只健康雄性SD大鼠(280~320g)依据数字表法随机分为3组:假手术组(Sham,n=3)、正常氧浓度组(Normoxia,n=6)和NBO(n=6)组,应用线栓法制备大鼠大脑中动脉阻塞模型,缺血90 min再灌注24 h。Sham组和Normoxia组大鼠术后呼吸普通空气,NBO组大鼠术后至再灌注前呼吸100%常压氧气。采用免疫荧光染色和Western blotting的检测方法,研究NBO治疗对脑缺血核心区炎性因子IL-1β、TNF-α和转录调节因子NF-κB及其抑制蛋白IκB表达的影响。结果免疫荧光结果显示:(1)与Sham组相比,Normoxia组缺血核心区IL-1β、TNF-α及核移位NF-κB p65阳性细胞数目明显增多(P<0.05),荧光强度增强;(2)与Normoxia组相比,NBO组缺血核心区IL-1β、TNF-α及核移位NF-κB p65阳性细胞数目明显减少(P<0.05),荧光强度减弱。Western blotting结果显示:(1)与Sham组相比,Normoxia组缺血核心区NF-κB p65显著升高,IκB明显降低(P<0.05),(2)与Normoxia组相比,NBO组缺血核心区NF-κB p65水平显著降低,IκB明显升高(P<0.05)。结论 NBO治疗可能通过调节缺血核心区转录调控因子NF-κB的适度活化来抑制脑缺血再灌注炎性损伤,从而实现脑神经保护作用。Objective To investigate the effect of normobaric hyperoxia （NBO） on expression of interleukin-1 β （IL- 1β）, tumor necrosis factor-α （TNF-α）, nuclear factor-κB （NF-κB） and inhibitor of NF-κB （IκB） induced by cerebral ischemia-reperfusion injury in rats, and explore the effect of NBO treatment on inflammatory injury mediated by NF-κB after cerebral ischemia. Methods A total of fifteen healthy adult male SD rats （280-320 g） were randomly divided into Sham group （ n =3）, normoxia group （ n =6） or NBO group （ n =6）. A model of middle cerebral artery occlusion for 90 min and reperfusion for 24 h was induced by using the intraluminal suture method. The sham group and the normoxia group rats breathed normal air, and NBO group rats were exposed to 100 % oxygen after ischemia until reperfusion. Immunofluorescence staining and Western blotting were used to observe the expression of IL-1β, TNF-α, NF-κB and IκB in the core cerebral ischemic region. Results Immunofluorescence results showed that： ①compared with Sham group, the number of IL-1β, TNF-α or nuclear NF-κB p65 positive cells in the core ischemic region of Normoxia group was increased significantly （ P 〈0.05） with the fluorescence intensity increased; ②compared with Normoxia group, the number of IL-1β, TNF-α or nuclear NF-κB p65 positive cells in the core ischemic region of NBO group decreased significantly （ P 〈0.05） with the fluorescence intensity decreased. Western blotting results showed that： ① compared with Sham group, the expression of NF-κB p65 increased and the expression of IκB decreased significantly in core ischemic region of Normoxia group （ P 〈0.05）; ②compared with Normoxia group, the expression of NF-κB p65 decreased and the expression of IκB increased significantly of NBO group （ P 〈0.05）. Conclusion NBO treatment may inhibit cerebral ischemia-reperfusion injury by regulating the activation of transcription factor NF-κB in core ischemic region, which i

关 键 词：脑缺血再灌注 常压高浓度氧 炎性反应 核转录因子-ΚB 

分 类 号：R743[医药卫生—神经病学与精神病学]