含溴结构域蛋白4加重高糖诱导的内皮细胞损伤机制探讨  

Mechanism of Bromodomain 4 Aggravates High Glucose-Induced Endothelial Cell Injury

作　　者：孙云龙 王喜甲 孟哲[1] 高路[1] SUN Yunlong;WANG Xijia;MENG Zhe;GAO Lu(Department of Cardiovascular Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院心血管内科,河南郑州450052

出　　处：《河南医学研究》2023年第22期4033-4037,共5页Henan Medical Research

基　　金：国家自然科学基金资助项目(81970201);河南省优秀青年科学基金项目(212300410076)。

摘　　要：目的 探讨含溴结构域蛋白4(BRD4)对高糖诱导的血管内皮细胞损伤的作用及机制。方法 培养脐静脉内皮细胞(HUVECs),分为对照组、高糖刺激组(HG)、BRD4沉默组(BRD4 siRNA组)、BRD4沉默的HG组(BRD4 siRNA+HG组)。采用ELISA法检测各组炎症细胞因子水平,采用试剂盒检测细胞内活性氧(ROS)水平,采用试剂盒检测各组超氧化物歧化酶2(SOD2)和谷胱甘肽过氧化物酶(Gpx)活性以及丙二醛(MDA)水平,采用一氧化氮(NO)检测试剂盒检测NO含量,采用免疫荧光染色检测核因子E2相关因子2(NRF2)的表达以及核转位情况。结果 对照组和BRD4 siRNA组细胞促炎症因子、ROS、MDA、NO水平、SOD2和Gpx活性、细胞活性、细胞凋亡数量、NRF2表达及核转位水平差异无统计学意义(P>0.05)。HG组及BRD4 siRNA+HG组细胞促炎症因子、ROS、MDA水平高于对照组,SOD2、Gpx、NO水平、细胞活性、NRF2表达以及核转位水平低于对照组,且BRD4 siRNA+HG组细胞促炎症因子、ROS、MDA水平低于HG组,SOD2、Gpx、NO水平、细胞活性、细胞NRF2表达以及核转位水平高于HG组(P<0.05)。HG组及BRD4 siRNA+HG组细胞凋亡数量多于对照组,与HG组相比,BRD4 siRNA+HG组细胞凋亡数量减少(P<0.05)。结论 BRD4通过抑制NRF2的核转位加重高糖诱导的内皮细胞损伤,BRD4可能参与糖尿病并发症的发生发展。Objective To investigate the effect and mechanism of Bromodomain 4(BRD4)on high glucose-induced vascular endothelial cell injury.Methods Human umbilical vein endothelial cells(HUVECs)were cultured,and the cells were divided into 4 groups:control group,high glucose stimulation group(HG),BRD4 silencing group(BRD4 siRNA group),and BRD4 silencing+HG group.ELISA was used to detect the secretion of inflammatory cytokines in each group.And kits were used to detect the levels of intracellular reactive oxygen species(ROS).Kits were used to detect the activities of superoxide dismutase 2(SOD2)and Gpx,and malondialdehyde(MDA)level.Nitric oxide(NO)content was detected by NO detection kit.Nuclear factor-E2-related factor 2(NRF2)expression and nuclear translocation were detected by immunofluorescence staining.Results There were no statistically significant differences between the control group and the BRD4 siRNA group in levels of pro-inflammatory factors,ROS,MDA,NO,activities of antioxidant enzymes SOD2 and Gpx,cell activity,number of cell apoptosis,NRF2 expression,and nuclear translocation level(P>0.05).The levels of pro-inflammatory factors,ROS,and MDA in the HG group and BRD4 siRNA+HG group were higher than those in the control group,while the levels of antioxidant enzymes SOD2,Gpx,NO,cell activity,NRF2 expression,and nuclear translocation were lower than those in the control group.In addition,the levels of pro-inflammatory factors,ROS,and MDA in the BRD4 siRNA+HG group were lower than those in the HG group,while the levels of SOD2,Gpx,NO,cell activity,cell NRF2 expression,and nuclear translocation were higher than those in the HG group(P<0.05).The number of apoptotic cells in the HG group and BRD4 siRNA+HG group was higher than that in the control group.Compared with the HG group,the number of apoptotic cells in the BRD4 siRNA+HG group decreased(P<0.05).Conclusion BRD4 aggravates high glucose induced endothelial cell injury by inhibiting nuclear translocation of NRF2.BRD4 may be involved in the occurrence and development

关 键 词：内皮细胞 高血糖 含溴结构域蛋白4 氧化应激 NF-E2相关因子2 

分 类 号：R318[医药卫生—生物医学工程]