依达拉奉对缺氧诱导脑血管内皮细胞损伤的影响及机制研究  

Effect and mechanism of edaravone on cerebral vascular endothelial cell damage induced by hypoxia

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作  者:辛卫云 曹利华[2] XIN Weiyun;CAO Lihua(Henan Hospital of Traditional Chinese Medicine/The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou Henan 450011,China;Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou Henan 450046,China)

机构地区:[1]河南省中医院/河南中医药大学第二附属医院,河南郑州450011 [2]河南中医药大学中医药科学院,河南郑州450046

出  处:《天津药学》2025年第1期1-6,19,共7页Tianjin Pharmacy

摘  要:目的明确依达拉奉调控核因子κB(NF-κB)信号通路对缺氧诱导脑血管内皮细胞损伤的影响。方法分离大鼠脑血管内皮细胞,分成Control、Model(缺氧处理)、Edaravone-10μmol/L(缺氧和10μmol/L依达拉奉处理)、Edaravone-20μmol/L(缺氧和20μmol/L依达拉奉处理)、Edaravone-40μmol/L(缺氧和40μmol/L依达拉奉处理)、Edaravone-40μmol/L+PMA(缺氧和40μmol/L依达拉奉、NF-κB信号激活剂PMA处理)组,以噻唑蓝(MTT)方法检测各组细胞增殖活性变化,运用流式细胞术分析各组细胞凋亡水平变化,试剂盒检测活性氧(ROS)、丙二醛(MDA)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,Western blot法检测半胱氨酸天冬氨酸蛋白酶(Caspase)-3、裂解的半脱氨酸天冬氨酸蛋白酶(C-Caspase)-3、Caspase-9、C-Caspase-9、p65蛋白表达。结果与Cotrol组比较,Model组脑血管内皮细胞凋亡水平增加,细胞增殖活性降低,细胞中C-Caspase-3、C-Caspase-9、p65、ROS、MDA、LDH表达水平升高,Caspase-3、Caspase-9、SOD、GSH-Px表达水平降低。与Model组比较,Edaravone-10μmol/L、Edaravone-20μmol/L、Edaravone-40μmol/L组脑血管内皮细胞凋亡水平逐渐降低,细胞增殖活性逐渐升高,细胞中C-Caspase-3、C-Caspase-9、p65、ROS、MDA、LDH表达水平逐渐降低,Caspase-3、Caspase-9、SOD、GSH-Px表达水平逐渐升高。与Edaravone-40μol/L组比较,Edaravone-40μmol/L+PMA组脑血管内皮细胞增殖活性降低,细胞凋亡率升高,C-Caspase-3、C-Caspase-9、p65、ROS、MDA、LDH表达增多,Caspase-3、Caspase-9、SOD、GSH-Px表达降低。结论依达拉奉通过抑制NF-κB信号减轻缺氧诱导脑血管内皮细胞损伤。Objective To clarify the effect of edaravone-regulated nuclear factor kappa-B(NF-κB)signaling pathway on hypoxia-induced cerebral vascular endothelial cell injury.Methods Rat cerebral vascular endothelial cells were isolated and divided into Control,Model(hypoxia treatment),Edaravone-10μmol/L(hypoxia and 10μmol/L edaravone treatment),Edaravone-20μmol/L(hypoxia and 20μmol/L edaravone treatment),Edaravone-40μmol/L(hypoxia and 40μmol/L edaravone treatment),Edaravone-40μmol/L+PMA(hypoxia and 40μmol/L edaravone,NF-κB signal activator PMA treatment)group.Methyl thiazolyl tetrazolium(MTT)method was used to detect changes in cell proliferation activity in each group;flow cytometry was used to analyze changes in cell apoptosis;the kits were used to detect levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px);Western blot method was used to detect the expression of cysteine aspartic protease(Caspase)-3,cleaved cysteine aspartic protease(C-Caspase)-3,Caspase-9 and C-Caspase-9 and p65 protein.Results Compared with the Control group,the apoptosis level of cerebral vascular endothelial cells in the Model group increased,the cell proliferation activity decreased,the expression levels of C-Caspase-3,C-Caspase-9,p65,ROS,MDA and LDH were increased,the expression levels of Caspase-3,Caspase-9,SOD and GSH-Px were decreased.Compared with the Model group,in the Edaravone-10μmol/L,Edaravone-20μmol/L,Edaravone-40μmol/L groups,the apoptosis level of cerebral vascular endothelial cells gradually decreased,and the cell proliferation activity gradually increased,the expression levels of C-Caspase-3,C-Caspase-9,p65,ROS,MDA and LDH gradually decreased,the expression levels of Caspase-3,Caspase-9,SOD and GSH-Px gradually increased.Compared with the Edaravone-40μmol/L group,in the Edaravone-40μmol/L+PMA group,the proliferation activity of cerebral vascular endothelial cells was reduced,the apoptosis rate was increased,and the expression o

关 键 词:依达拉奉 NF-κB信号 脑血管内皮细胞 缺氧 

分 类 号:R743[医药卫生—神经病学与精神病学]

 

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