circHIPK2调节miR-7-5p/TCF4轴对血管紧张素Ⅱ诱导的血管内皮细胞凋亡的影响  

Effect of circHIPK2 on angiotensinⅡ-induced apoptosis of vascular endothelial cells through regulation of the miR-7-5p/TCF4 axis

作　　者：谷君[1] 任卫东[1] 李会贤[2] 邓文娟[1] 胡利梅[1] 刘慧颖[1] 蔡裕 GU Jun;REN Weidong;LI Huixian;DENG Wenjuan;HU Limei;LIU Huiying;CAI Yu(Department of Endocrinology,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院内分泌科,河北张家口075000 [2]河北北方学院附属第一医院心血管内科,河北张家口075000

出　　处：《中国医科大学学报》2025年第3期257-261,267,共6页Journal of China Medical University

基　　金：河北省医学科学研究课题计划(20190875);张家口市科学技术研究与发展计划(1911021D-7)。

摘　　要：目的研究环状RNA同源域相互作用蛋白激酶2(circHIPK2)调节miR-7-5p/转录因子4(TCF4)轴对血管紧张素Ⅱ(AngⅡ)诱导的血管内皮细胞凋亡的影响。方法将人脐静脉内皮细胞(HUVEC)随机分为对照组、模型组、阴性对照共转染组、敲低circHIPK2组、过表达miR-7-5p组、敲低circHIPK2+敲低miR-7-5p组。除对照组外,其余各组给予10 nmol/L AngⅡ,构建高血压损伤模型,转染后测定circHIPK2、miR-7-5p和TCF4 mRNA表达水平;检测细胞增殖、凋亡、线粒体膜电位、活性氧(ROS)表达、抗氧化酶活性、促炎性细胞因子水平、凋亡相关蛋白和TCF4蛋白表达水平。结果与对照组相比,模型组细胞circHIPK2和TCF4 mRNA表达水平、凋亡率、ROS相对表达、IL-6水平、IL-1β水平、IL-18水平、Bax和TCF4蛋白表达水平升高(P<0.05),细胞活力、miR-7-5p mRNA表达水平、线粒体膜电位、超氧化物歧化酶(SOD)和过氧化氢酶活性、Bcl-2蛋白表达水平降低(P<0.05);敲低circHIPK2、过表达miR-7-5p均可逆转上述AngⅡ诱导的血管内皮细胞病理变化。敲低miR-7-5p可降低敲低circHIPK2对模型组细胞病理变化的改善作用。结论敲低circHIPK2可通过上调miR-7-5p表达而减弱TCF4表达,进而降低AngⅡ诱导的血管内皮细胞炎症和氧化应激水平,最终抑制细胞凋亡。Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotransfection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L AngⅡto establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial membrane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P<0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed AngⅡ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing AngⅡ-induced inflammation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.

关 键 词：环状RNA同源域相互作用蛋白激酶2 miR-7-5p/TCF4轴 血管紧张素Ⅱ 血管内皮细胞 凋亡 

分 类 号：R589[医药卫生—内分泌]