外源性一氧化碳释放分子经NF-κB通路对脑出血大鼠炎性反应及神经功能的影响  

Effects of CORM-2 on Inflammatory Response and Neurological Function in Rats with Cerebral Hemorrhage Via NF-κB Pathway

作　　者：周君[1] 吴勤花[1] 夏翠萍[1] ZHOU Jun;WU Qinhua;XIA Cuiping(South Hospital of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 201406,China)

机构地区：[1]上海交通大学附属第六人民医院南院,上海201406

出　　处：《药品评价》2023年第1期23-28,共6页Drug Evaluation

基　　金：上海市奉贤区科技发展基金医学类(20191301)。

摘　　要：目的分析外源性一氧化碳释放分子(CORM-2)经核因子κB(NF-κB)通路对脑出血大鼠炎性反应及神经功能的影响。方法使用自体股动脉血注射法成功制备150只SD雄性大鼠脑出血模型,依据随机数表法分为A组(单纯脑出血)、B组(CORM-2+脑出血)、C组(iCORM-2+脑出血)、D组(CORM-2+PDTC+脑出血)、E组(iCORM-2+PDTC+脑出血),各30只,并纳入30只健康SD雄性大鼠设置F组(假手术组)。以建模后6 h、12 h、7 d为观察点(每个时间段各10只大鼠,各组各时间点均分为各组亚组,如A组6 h为A1组,A组12 h为A2组,A组7 d为A3组,其他组分组方法相同)。比较各组大鼠不同时刻的旷场实验及热板测痛法结果,并比较各组大鼠不同时刻脑组织中一氧化碳含量、灶周损伤组织细胞质中IκB激酶(Iκκ)、磷酸化IκB激酶(p-Iκκ)、核因子κB亚基p65(NF-κB p65)、磷酸化核因子κB亚基p65(p-NF-κB p65)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)表达水平。结果对相同时间点的不同组大鼠进行比较,以A1-F1组大鼠为例,F1组大鼠的旷场实验总运动距离、平均速度、跨越区域的次数、总转圈次数均多于其他各组,F1组大鼠的热痛缩足潜伏期最长,其次为D1组,再次为B1组和E1组,A1组和C1组最少;F1组大鼠的脑组织中一氧化碳含量最低,F1组大鼠的灶周损伤组织细胞质中Iκκ、p-Iκκ、NF-κB p65、p-NF-κB p65水平最低,F1组大鼠的灶周损伤组织细胞质中TNF-α、IL-1β水平最低,其次为D1组,再次为B1组和E1组,A1组和C1组最高,差异有统计学意义(P<0.05)。且A2-F2组和A3-F3组间大鼠上述指标比较结果与A1-F1组大小趋势相同。结论CORM-2可能通过抑制Iκκ/NF-κB信号通路活性缓解脑出血大鼠的炎性损伤,保护了其神经功能。Objective To analyze the effect of exogenous CO release molecule(CORM-2)via nuclear factorκB(NF-κB)pathway on inflammatory response and neurological function in rats with cerebral hemorrhage.Methods 150 SD male rats with cerebral hemorrhage were successfully prepared by autologous femoral arterial blood injection.They were divided into group A(simple cerebral hemorrhage),group B(CORM-2+cerebral hemorrhage),group C(iCORM-2+cerebral hemorrhage),group D(CORM-2+PDTC+cerebral hemorrhage)and group E(iCORM-2+PDTC+cerebral hemorrhage)according to random number table method,with 30 patients each.Thirty healthy male SD rats were included in the F group(sham operation group).Taking 6 h,12 h,and 7 d after modeling as observation points(10 rats at each time point,each group was divided into subgroups at each time point,for example,group A 6 h was group A1,group A 12h was group A2,group A 7 d was group A3,and other groups were grouped in the same way).The results of open field experiment and hot plate pain measurement were compared in each groupsat different time.The levels of CO in brain tissue,IκB kinase(Iκκ),phosphorylated IκB kinase(p-Iκκ),nuclear factor-κB subunit p65(NF-κB p65)and phosphorylated nuclear factor-κB subunit p65(p-NF-κBp65)in the cytoplasm of perifocal injured tissue were compared between the groups at different time points,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)expression levels.Results Different groups of rats at the same time point were compared.Taking the rats in group A1-F1 as an example,the total movement distance,average speed,number of crossing areas and total number of turning in the open field experiment of rats in group F1 were higher than those in other groups.The incubation period of heat pain foot contraction of rats in group F1 was the longest,followed by group D1,group B1 and group E1,and group A1 and group C1 were the least.The content of carbon monoxide in the brain tissue of rats in F1 group was the lowest,the levels of Iκκ,p-Iκκ,NF-κB p65 and p-NF-κBp65

关 键 词：脑出血 外源性一氧化碳释放分子 核因子κB通路 炎性反应 神经功能 SD大鼠 

分 类 号：R743.34[医药卫生—神经病学与精神病学]