Effect of finerenone on apoptosis and oxidative stress of rat myocardial H9C2 cells induced by lipopolysaccharide and its mechanism

ZHANG Heng; DENG Wei

doi:10.14188/j.1671-8852.2024.0386

您当前的位置：

首页 >

文章列表页 >

Effect of finerenone on apoptosis and oxidative stress of rat myocardial H9C2 cells induced by lipopolysaccharide and its mechanism

更新时间：2026-11-05

- Effect of finerenone on apoptosis and oxidative stress of rat myocardial H9C2 cells induced by lipopolysaccharide and its mechanism
- Medical Journal of Wuhan University Vol. 46, Issue 6, Pages: 703-708(2025)
- 作者机构：
  
  1.武汉大学人民医院心血管内科
  2.代谢与相关慢病湖北省重点实验室湖北武汉 430060
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0386
  CLC： R542.2⁺1
- Received：18 May 2024，
  
  Published：25 June 2025
- 稿件说明：
移动端阅览
张恒,邓伟.非奈利酮对脂多糖诱导的大鼠心肌H9C2细胞凋亡和氧化应激的影响及作用机制[J].武汉大学学报（医学版）,2025,46(06):703-708.

ZHANG Heng,DENG Wei.Effect of finerenone on apoptosis and oxidative stress of rat myocardial H9C2 cells induced by lipopolysaccharide and its mechanism[J].Medical Journal of Wuhan University,2025,46(06):703-708.
张恒,邓伟.非奈利酮对脂多糖诱导的大鼠心肌H9C2细胞凋亡和氧化应激的影响及作用机制[J].武汉大学学报（医学版）,2025,46(06):703-708. DOI： 10.14188/j.1671-8852.2024.0386.

ZHANG Heng,DENG Wei.Effect of finerenone on apoptosis and oxidative stress of rat myocardial H9C2 cells induced by lipopolysaccharide and its mechanism[J].Medical Journal of Wuhan University,2025,46(06):703-708. DOI： 10.14188/j.1671-8852.2024.0386.

摘要

目的

分析非奈利酮（Finerenone）对大鼠心肌H9C2细胞在脂多糖（LPS）刺激下引起的凋亡和氧化应激的影响及其作用机制。

方法

使用不同浓度的非奈利酮（0

2.5

20 mmol·L

-1

）经过24 h的处理，接着给予12 h的脂多糖（10 µg·mL

-1

）刺激，使用CCK⁃8试剂盒评估细胞活性，并确定适宜的非奈利酮浓度以进行后续研究。将大鼠心肌H9C2细胞随机分成4组：对照组、仅非奈利酮处理组（浓度为5 mmol·L

-1

）、单独LPS处理组（浓度为10 µg·mL

-1

）以及同时接受LPS和非奈利酮处理组（浓度分别为10 µg·mL

-1

和5 mmol·L

-1

）。使用活性氧(ROS)检测试剂盒评估细胞的氧化应激水平，一步法TUNEL细胞凋亡检测试剂盒检测细胞凋亡；Western Blot法检测C⁃caspase⁃3、Bax、Bcl⁃2、PI3K、AKT和GSK⁃3β表达水平。

结果

不同浓度的非奈利酮处理后，对大鼠心肌H9C2细胞的存活率差异无统计意义（

0.05）。给予非奈利酮处理可挽救由LPS刺激诱导的细胞存活率下降，在非奈利酮浓度为5、10、20 mmol·L

-1

的组中，差异具有统计学意义（

0.05）。LPS组细胞凋亡、氧化应激显著高于对照组(

0.05)；非奈利酮处理后能抑制LPS诱导的凋亡因子的表达(

0.05)，同时减轻凋亡和氧化应激的水平(

0.05)。机制方面，Western Blot显示非奈利酮能激活PI3K/AKT/GSK⁃3β信号通路。

结论

非奈利酮能减轻LPS诱导的细胞毒性，抑制凋亡和氧化应激，而这些作用可能是通过激活PI3K/AKT/GSK⁃3β信号通路实现的。

Abstract

Objective

To investigate the mechanism of action of finerenone and its effect on oxidative stress and apoptosis in rat myocardial H9C2 cells stimulated with lipopolysaccharide (LPS).

Methods

Following a 24⁃hour course of therapy with varying finerenone concentrations (0

2.5

and 20 mmol·

-1

) followed by 12 hours of LPS (10 µg·mL

-1

) stimulation

cellular activity was assessed using a CCK⁃8 kit

and the appropriate finerenone concentration was determined for subsequent studies. Rat myocardial H9C2 cells were randomly divided into four groups: a control group

a finerenone⁃treated group only (at a concentration of 5 mmol·L

-1

)

an LPS⁃treated group alone (at a concentration of 10 µg·mL

-1

)

and a group that received both LPS and finerenone treatment (at concentrations of 10 µg·mL

-1

and 5 mmol·L

-1

respectively). Oxidative stress levels in cells were assessed using a reactive oxygen species （ROS） assay kit

a one⁃step TUNEL apoptosis assay kit to assess apoptosis levels; and Western Blot was adopted to detect C⁃caspase⁃3

Bax

Bcl⁃2

PI3K

AKT

and GSK⁃3β expression levels.

Results

There was no statistically significant difference in the survival of rat myocardial H9C2 cells after treatment with different concentrations of finerenone (

0.05). Administration of finerenone treatment rescued the decline in cell survival induced by LPS stimulation

and the difference was statistically significant in the groups with finerenone treatment at concentrations of 5

and 20 mmol·L

-1

(

0.05). When compared to the control group

the LPS group showed noticeably higher levels of oxidative stress and apoptosis. It was discovered that finerenone treatment reduced the amount of apoptotic proteins produced in response to LPS (

0.05)

and at the same time attenuated the levels of apoptosis and oxidative stress (

0.05). Mechanistically

Western Blot showed that finerenone activated the PI3K/AKT/GSK⁃3β signaling pathway.

Conclusion

Finerenone attenuates LPS⁃induced cytotoxicity and inhibits apoptosis and oxidative stress

and these effects may be achieved by activating the PI3K/AKT/GSK⁃3β signaling pathway.

关键词

Keywords

references

SEYMOUR C , LIU V , IWASHYNA T , et al . Assessment of clinical criteria for sepsis: For the third international consensus definitions for sepsis and septic shock (sepsis⁃3) [J ] . JAMA , 2016 , 315 ( 8 ): 801 ⁃ 810 .

CARBONE F , LIBERALE L , PREDA A , et al . Septic cardiomyopathy: From pathophysiology to the clinical setting [J ] . Cells , 2022 , 11 ( 18 ): 2833 .

GERISCH M , HEINIG R , ENGELEN A , et al . Biotransformation of fi nerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, in dogs, rats, and humans, in vivo and in vitro [J ] . Drug Metab Dispos , 2018 , 46 ( 11 ): 1546 ⁃ 1555 .

AGARWAL R , KOLKHOF P , BAKRIS G , et al . Steroidal and non⁃steroidal mineralocorticoid receptor antagonists in cardiorenal medicine [J ] . Eur Heart J , 2021 , 42 ( 2 ): 152 ⁃ 161 .

LV R L , XU L L , CHE L , et al . Cardiovascular⁃renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus [J ] . Front Endocrinol , 2023 , 14 : 1125693 .

HOLLENBERG S M , SINGER M . Pathophysiology of sepsis⁃induced cardiomyopathy [J ] . Nat Rev Cardiol , 2021 , 18 ( 6 ): 424 ⁃ 434 .

FENG M , ZHENG C , LI X , et al . Reversal of lipopolysaccharide⁃induced cardiomyocyte apoptosis via α7nAChR by dexmedetomidine [J ] . Cell Mol Biol (Noisy⁃le⁃grand) , 2024 , 70 ( 5 ): 127 ⁃ 131 .

ZHAO H , LIN X , CHEN Q , et al . Quercetin inhibits the NOX2/ROS⁃mediated NF⁃κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis⁃induced cardiomyopathy [J ] . Toxicol Appl Pharmacol , 2023 , 477 : 116672 .

PEI X B , LIU B . Research progress on the mechanism and management of septic cardiomyopathy: A comprehensive review [J ] . Emerg Med Int , 2023 , 2023 : 8107336 .

LU N F , NIU H X , LIU A Q , et al . Types of septic cardiomyopathy: Prognosis and influencing factors–A clinical study [J ] . Risk Manag Healthc Policy , 2024 , 17 : 1015 ⁃ 1025 .

BAKRIS G L , AGARWAL R , ANKER S D , et al . Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes [J ] . N Engl J Med , 2020 , 383 ( 23 ): 2219 ⁃ 2229 .

KOLKHOF P , JAISSER F , KIM S Y , et al . Steroidal and novel non⁃steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: Comparison at bench and bedside [J ] . Handb Exp Pharmacol , 2017 , 243 : 271 ⁃ 305 .

FRUMAN D A , CHIU H , HOPKINS B D , et al . The PI3K pathway in human disease [J ] . Cell , 2017 , 170 ( 4 ): 605 ⁃ 635 .

GHAFFARI⁃NASAB A , GHIASI F , KEYHANMANESH R , et al . Bone marrow⁃derived c⁃kit positive stem cell administration protects against diabetes⁃induced nephropathy in a rat model by reversing PI3K/AKT/GSK⁃3β pathway and inhibiting cell apoptosis [J ] . Mol Cell Biochem , 2024 , 479 ( 3 ): 603 ⁃ 615 .

LUO H , SONG B , XIONG G , et al . Cadmium inhibits neural stem/progenitor cells proliferation via MitoROS⁃dependent AKT/GSK⁃3β/β⁃catenin signaling pathway [J ] . J Appl Toxicol , 2021 , 41 ( 12 ): 1998 ⁃ 2010 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Tectorigenin alleviates doxorubicin‐induced cardiotoxicity through activating SIRT1/FOXO1 signaling pathway

Hesperetin alleviates high glucose and high lipid induced mitochondrial damage and apoptosis in AC16 cardiomyocytes via the AMPKα/SIRT1/PGC‐1α signaling pathway

LAPTM5 protects against doxorubicin⁃induced cardiotoxicity by inhibiting ferroptosis

Effects of High Glucose on the Proliferation and Apoptosis of Endothelial Progenitor Cells and Their Relationship with Oxidative Stress

Comparative clinical efficacy of different acid formulations in the treatment of scalp seborrheic dermatitis

Related Author

ZHANG Heng

DENG Wei

HU Xiaoli

LEI Ji

LI Jiahao

YUAN Xiaopin

XU Feixue

ZHANG Meng

Related Institution

Department of Cardiology, Gucheng Hospital Affiliated to Hubei University of Arts and Science, Xiangyang

Department of Cardiology, Second Hospital of Tianjin Medical University & Tianjin Key Laboratory of Ionic‐Molecular Function of Cardiovascular Disease

Department of Cardiology, Renmin Hospital of Wuhan University & Hubei Key Laboratory of Metabolic and Chronic Diseases

Department of Cardiology, Renmin Hospital of Wuhan University & Hubei Key Laboratory of Metabolic and Related Chronic Diseases

武汉大学人民医院心内科

AI问答

⁰