Ang-Ⅱ介导的铁死亡参与房颤触发及心衰进展的机制研究  

Mechanism Study on Ang-ⅡMediated Ferroptosis in Triggering Atrial Fibrillation and Progression of Heart Failure

作　　者：王欣婷 徐萌萌 孔雪 冯洪亮 杨建 WANG Xinting;XU Mengmeng;KONG Xue(Jining Third People's Hospital/Jining Yanzhou District People's Hospital,Shandong Jining 272000,China)

机构地区：[1]山东省济宁市第三人民医院/济宁市兖州区人民医院心血管内科,山东济宁272000

出　　处：《河北医学》2024年第6期886-892,共7页Hebei Medicine

基　　金：山东省医药卫生科技项目,(编号:20230301072Q)。

摘　　要：目的:探讨赖氨酸脱甲基酶5B(KDM5B)/增强激活转录因子3(ATF3)信号通路在血管紧张素Ⅱ(Ang-Ⅱ)诱导心脏肥大中的作用。方法:将小鼠心肌细胞HL-1分为以下处理组:对照组、Ang-Ⅱ组、Ang-Ⅱ+Lv-NC组、Ang-Ⅱ+Lv-KDM5B组和Ang-Ⅱ+Lv-KDM5B KD组。通过蛋白质印迹分析各组细胞中KDM5B、ATF3蛋白表达。通过荧光染色检测细胞内α-肌动蛋白(α-SMA)、Fe^(2+)和活性氧(ROS)水平。结果:与Ang-Ⅱ+Lv-NC组相比,Ang-Ⅱ+Lv-KDM5B组中HL-1细胞中KDM5B蛋白表达显著增加(P<0.05),和ATF3蛋白表达显著降低(P<0.05),而Ang-Ⅱ+Lv-KDM5B KD组中HL-1细胞中KDM5B蛋白表达显著降低(P<0.05),和ATF3蛋白表达显著增加(P<0.05)。与对照组相比,Ang-Ⅱ组和Ang-Ⅱ+Lv-NC组相对细胞大小、细胞内相对Fe^(2+)荧光强度、相对ROS荧光强度显著增加(P<0.05),和相对细胞活力显著降低(P<0.05)。与Ang-Ⅱ+Lv-NC组相比,Ang-Ⅱ+Lv-KDM5B组相对细胞大小、细胞内相对Fe^(2+)荧光强度、相对ROS荧光强度显著增加(P<0.05),和Ang-Ⅱ+Lv-KDM5B KD组相对细胞大小、细胞内相对Fe^(2+)荧光强度、相对ROS荧光强度显著降低(P<0.05)。结论:KDM5B/ATF3驱动Ang-Ⅱ诱导的心肌肥大的进展,并促进对肥大性应激反应相关的铁死亡。Objective:To investigate the role of lysine demethylase 5B(KDM5B)/enhanced activated transcription factor 3(ATF3)signaling pathway in angiotensinⅡ(Ang-Ⅱ)-induced cardiac hypertrophy.Methods:Mouse cardiomyocytes HL-1 were divided into the following treatment groups:control group,Ang-Ⅱgroup,Ang-Ⅱ+Lv-NC group,Ang-Ⅱ+Lv-KDM5B group and Ang-Ⅱ+LV-KDM5KD group.The expression of KDM5B and ATF3 protein in cells of each group was analyzed by protein blot.The intracellular levels ofα-actin(α-SMA),Fe^(2+)and reactive oxygen species(ROS)were detected by fluorescence staining.Results:Compared with Ang-Ⅱ+Lv-NC group,the expression of KDM5B protein in HL-1 cells in Ang-Ⅱ+Lv-KDM5B group increased significantly(P<0.05),and the expression of ATF3 protein decreased significantly(P<0.05),while the expression of KDM5B protein in HL-1 cells in Ang-Ⅱ+Lv-KDM5B KD group decreased significantly(P<0.05).Compared with the control group,the relative cell size,intracellular relative Fe^(2+)fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱgroup and Ang-Ⅱ+Lv-NC group increased significantly(P<0.05),and the relative cell viability decreased significantly(P<0.05).Compared with Ang-Ⅱ+Lv-NC group,the relative cell size,intracellular relative Fe^(2+)fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱ+Lv-KDM5B group increased significantly(P<0.05),while the relative cell size,intracellular relative Fe^(2+)fluorescence intensity and relative ROS fluorescence intensity in Ang-Ⅱ+Lv-KDM5B KD group decreased significantly(P<0.05).Conclusion:KDM5B/ATF3 drives the progress of Ang-Ⅱ-induced myocardial hypertrophy and promotes ferroptosis related to hypertrophic stress response.

关 键 词：赖氨酸脱甲基酶5B 增强激活转录因子3 血管紧张素Ⅱ 

分 类 号：R541.75[医药卫生—心血管疾病] R541.6[医药卫生—内科学]