Micro-ribonucleic acid 101-3p induces ferroptosis in cardiomyocytes of mice with heart failure by inhibiting dual specificity phosphatase 1

MENG Suyan; ZHANG Lin; MA Liang

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Micro-ribonucleic acid 101-3p induces ferroptosis in cardiomyocytes of mice with heart failure by inhibiting dual specificity phosphatase 1

更新时间：2026-06-10

- Micro-ribonucleic acid 101-3p induces ferroptosis in cardiomyocytes of mice with heart failure by inhibiting dual specificity phosphatase 1
- Journal of Chongqing Medical University Pages: 1-7(2026)
- 作者机构：
  
  山西省心血管病医院/山西省心血管病研究所公共卫生科，太原 030027
- 作者简介：
- 基金信息：
- DOI：
  CLC： R541
- Received：09 December 2025，
  
  Revised：2026-03-10，
  
  Accepted：26 March 2026，
  
  Online First：10 June 2026，
- 稿件说明：
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MENG Suyan,ZHANG Lin,MA Liang.Micro-ribonucleic acid 101-3p induces ferroptosis in cardiomyocytes of mice with heart failure by inhibiting dual specificity phosphatase 1[J].Journal of Chongqing Medical University,
DOI：

MENG Suyan,ZHANG Lin,MA Liang.Micro-ribonucleic acid 101-3p induces ferroptosis in cardiomyocytes of mice with heart failure by inhibiting dual specificity phosphatase 1[J].Journal of Chongqing Medical University, DOI：10.13406/j.cnki.cyxb..

摘要

目的

探讨微小核糖核酸-101-3p（micro ribonucleic acid-101-3p，miR-101-3p）对心力衰竭（heart failure，HF）小鼠心肌细胞铁死亡的影响及机制。

方法

采用横向主动脉缩窄（transverse aortic constriction，TAC）术构建HF小鼠模型。将小鼠随机分为6组：假手术组、TAC组（接受TAC手术）、TAC+antagomir-NC组、TAC+antagomir-101-3p组、antagomir-101-3p+sh-NC组、antagomir-101-3p+sh-双特异性磷酸酶1（dual specificity phosphatase 1，DUSP1）组，每组10只。末次干预后，超声心动图检测小鼠心功能；实时荧光定量聚合酶链式反应（real-time quantitative polymerase chain reaction，qRT-PCR）检测miR-101-3p、DUSP1信使核糖核酸（messenger ribonucleic acid，mRNA）表达；蛋白质印迹检测DUSP1蛋白表达；苏木精-伊红（hematoxylin and eosin，HE）染色观察心肌组织病理损伤；试剂盒检测心肌组织铁死亡标志物Fe

、丙二醛（malondialdehyde，MDA）、谷胱甘肽（glutathione，GSH）和谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）水平；分离原代心肌细胞进行荧光素酶报告基因实验。

结果

与假手术组相比，TAC组小鼠心肌组织miR-101-3p的表达明显升高（

0.05），左室射血分数（left ventricular ejection fraction，LVEF）、短轴缩短率（fractional shortening，FS）、GSH、GPX4、DUSP1均明显降低（

0.05），室间隔（interventricular septum，IVS）、左心室后壁厚度（left ventricular posterior wall，LVPW）、左心室心肌质量/体质量（left ventricular myocardial mass/body weight，LV mass/BW）、心肌组织横截面积百分比以及Fe

、MDA水平明显升高（P

0.05）。与TAC+antagomir-NC组相比，TAC+antagomir-101-3p组小鼠心肌组织miR-101-3p表达明显降低（

0.05），LVEF、FS、GSH、GPX4、DUSP1明显升高（

0.05），IVS、LVPW、LV mass/BW、心肌组织横截面积百分比以及Fe

、MDA水平明显降低（

0.05）。sh-DUSP1部分逆转了antagomir-101-3p对HF小鼠的改善作用（

0.05）。荧光素酶报告基因实验显示，miR-101-3p可靶向抑制DUSP1。

结论

抑制miR-101-3p通过上调心肌组织中DUSP1的表达抑制心肌细胞铁死亡，从而缓解小鼠HF。

Abstract

Objective

To investigate the effect and mechanism of micro-ribonucleic acid 101-3p（miR-101-3p） on ferroptosis in cardiomyocytes of mice with heart failure（HF）.

Methods

Transverse aortic constriction（TAC） surgery was performed to establish a mice model of HF. The mice were randomly divided into sham-operation group，TAC group （treated with TAC surgery），TAC+antagomir-NC group，TAC+antagomir-101-3p group，antagomir-101-3p+sh-NC group，and antagomir-101-3p+sh-dual specificity phosphatase 1（DUSP1） group，with 10 mice in each group. After the last intervention，echocardiography was used to assess cardiac function；qRT-PCR was used to measure the mRNA expression levels of miR-101-3p and DUSP1，and Western blot was used to measure the protein expression level of DUSP1；HE staining was used to observe pathological injury in myocardial tissue； kits were used to measure the levels of ferroptosis markers in myocardial tissue，including Fe

，malondialdehyde（MDA），glutathione（GSH），and glutathione peroxidase 4（GPX4）；primary cardiomyocytes were isolated for luciferase reporter assay.

Results

Compared with the sham-operation group，the TAC group had a significant increase in the expression level of miR-101-3p in myocardial tissue and significant reductions in left ventricular ejection fraction（LVEF），fractional shortening（FS），GSH，GPX4，and DUSP1（

0.05），as well as significant increases in interventricular septum（IVS），left ventricular posterior wall（LVPW） thickness，left ventricular mass/body weight（LV mass/BW），the percentage of myocardial cross-sectional area，and the levels of Fe

and MDA（

0.05）. Compared with the TAC+antagomir-NC group，the TAC+antagomir-101-3p group had a significant reduction in the expression level of miR-101-3p in myocardial tissue （

0.05） and significant increases in LVEF，FS，GSH，GPX4，and DUSP1（

0.05），as well as significant reductions in IVS，LVPW，LV mass/BW，the perce

ntage of myocardial cross-sectional area，and the levels of Fe

and MDA（

0.05）. The results showed that sh-DUSP1 partially reversed the improvement effect of antagomir-101-3p on HF mice（

0.05）. Luciferase reporter assay showed that miR-101-3p could target and inhibit DUSP1.

Conclusion

Inhibiting miR-101-3p can alleviate HF in mice by upregulating the expression of DUSP1 in myocardial tissue and inhibiting cardiomyocyte ferroptosis.

关键词

Keywords

references

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