[1]井晨阳,张思捷,李宁荫.铁死亡在雌二醇/睾酮比例失衡条件下血管紧张素Ⅱ诱导心肌损害中的相关作用[J].陕西医学杂志,2026,(4):440-445.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.002]
　JING Chenyang,ZHANG Sijie,LI Ningyin.Role of iron death in myocardial damage induced by angiotensin Ⅱ in the context of estradiol/testosterone ratio imbalance[J].,2026,(4):440-445.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.002]
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铁死亡在雌二醇/睾酮比例失衡条件下血管紧张素Ⅱ诱导心肌损害中的相关作用

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年4期
页码:
440-445
栏目:
基础研究
出版日期:
2026-04-05

文章信息/Info

Title:
Role of iron death in myocardial damage induced by angiotensin Ⅱ in the context of estradiol/testosterone ratio imbalance
作者:
井晨阳1; 张思捷1; 李宁荫2
（1.兰州大学第二医院/第二临床医学院，甘肃 兰州 730000，2.兰州大学第二医院心血管内科，甘肃 兰州 730000）
Author(s):
JING Chenyang1 ; ZHANG Sijie1 ; LI Ningyin2
（1.The Second Hospital of Lanzhou University/Second Clinical Medical College,Lanzhou 730000,China；2.Department of Cardiology,The Second Hospital of Lanzhou University,Lanzhou 730000,China）
关键词:
绝经; 高血压; 心肌损害; 铁死亡; 氧化应激; 细胞活性
Keywords:
Menopause; Hypertension; Myocardial damage; Ferroptosis; Oxidative stress; Cell viability
分类号:
R 542.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.002
文献标志码:
A
摘要:
目的：探讨铁死亡在绝经后高血压心肌细胞损害中发挥的重要作用。方法：体外培养H9C2细胞，将其分为四组。对照组：无药物干预；血管紧张素Ⅱ（AngⅡ）组：1×10-6 μmol/L的AngⅡ干预24 h；雌二醇（E2）/睾酮（T）（E2/T）组：1×10-6 μmol/L的E2/1×10-7 μmol/L的T干预24 h；AngⅡ+E2/T组：同时用1×10-6 μmol/L的AngⅡ及1×10-6 μmol/L的E2/1×10-7 μmol/L的T干预24 h。通过CCK-8检测细胞活性，免疫荧光法检测活性氧（ROS）水平，采用丙二醛（MDA）试剂盒检测MDA水平，蛋白质印迹法检测心房钠利尿肽（ANP）与B型钠利尿肽（BNP）表达水平，蛋白质印迹（Western blot）法及定量实时荧光PCR（RTqPCR）法检测谷胱甘肽过氧化物酶4（GPX4）、核因子红细胞2相关因子2（Nrf2）表达水平。结果：①细胞活性：AngⅡ+E2/T干预组H9C2细胞活性相较其他各组细胞活性均显著下降（均P<0.001）；②ROS水平：在四组中，AngⅡ+E2/T干预组H9C2细胞ROS水平明显升高（P<0.05）；③心肌损害程度：四组间AngⅡ+E2/T干预组H9C2细胞ANP、BNP蛋白表达水平增高（P<0.05、P<0.001）；④铁死亡水平：与其他三组比较，AngⅡ+E2/T共同干预组MDA、Nrf2水平升高（P<0.05、P<0.001），GPX4水平下降（P<0.0001）。结论：在绝经后高血压所致心肌损害中随着氧化应激水平升高，铁死亡水平呈同向升高，由此推测铁死亡在绝经后高血压心肌损害中扮演重要角色，下调铁死亡水平或将成为临床预防及治疗绝经后高血压心肌损害的新靶点。
Abstract:
Objective:To investigate the important role of ferroptosis in myocardial cell damage induced by postmenopausal hypertension.Methods：H9C2 cells were cultured in vitro and divided into 4 groups：control group （no drug intervention）;angiotensin Ⅱ （AngⅡ） group （intervention with 1×10-6 μmol/L AngⅡ for 24 h）;estradiol （E2）/testosterone （T） （E2/T） group （intervention with 1×10-6 μmol/L E2 and 1×10-7 μmol/L T for 24 h）;AngⅡ+E2/T group （simultaneous intervention with 1×10-6 μmol/L Ang Ⅱ,1×10-7 μmol/L E2 and 1×10-7 μmol/L T for 24 h）.Cell viability was detected by CCK-8 assay,reactive oxygen species （ROS） levels by immunofluorescence,malondialdehyde （MDA） levels by MDA kit,protein expressions of atrial natriuretic peptide （ANP） and Btype natriuretic peptide （BNP） by Western blot,and expressions of glutathione peroxidase 4 （GPX4） and nuclear factor erythroid 2related factor 2 （Nrf2） by Western blot and realtime quantitative PCR （RTqPCR）.Results:Cell viability：The viability of H9C2 cells in the AngⅡ+E2/T group was significantly decreased compared with that in other groups （all P<0.001）;ROS levels：Among the 4 groups,ROS levels in H9C2 cells of the AngⅡ+E2/T group were significantly increased （P<0.05）;Myocardial damage degree：The protein expressions of ANP and BNP in H9C2 cells of the AngⅡ+E2/T group were increased compared with other groups （P<0.05,P<0.001）;Ferroptosis levels：Compared with the other 3 groups,MDA and Nrf2 levels in the AngⅡ+E2/T group were increased （P<0.05,P<0001）,while GPX4 level was decreased （P<0.0001）.Conclusion:In myocardial damage caused by postmenopausal hypertension,ferroptosis levels increase in parallel with the elevation of oxidative stress,suggesting that ferroptosis plays an important role in postmenopausal hypertensive myocardial damage.Downregulating ferroptosis levels may become a new target for clinical prevention and treatment of postmenopausal hypertensive myocardial damage.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82160137）；兰州市科技计划项目（2023240）
更新日期/Last Update: 2026-04-05