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

HU Xiaoli; LEI Ji; LI Jiahao; YUAN Xiaopin

doi:10.14188/j.1671-8852.2025.1181

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

更新时间：2026-11-05

- Tectorigenin alleviates doxorubicin‐induced cardiotoxicity through activating SIRT1/FOXO1 signaling pathway
- Medical Journal of Wuhan University Vol. 47, Issue 10, Pages: 1310-1317(2026)
- 作者机构：
  
  1.湖北文理学院附属谷城医院心血管内科湖北襄阳 441700
  2.天津医科大学第二医院心血管内科/天津市心血管病离子与分子机能重点实验室天津 300211
  3.武汉大学人民医院心血管内科/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.1671-8852.2025.1181
  CLC： R54
- Received：13 October 2025，
  
  Published：25 October 2026
- 稿件说明：
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胡小丽,雷霁,李佳昊等.鸢尾苷元通过激活SIRT1/FOXO1信号通路减轻阿霉素心肌毒性[J].武汉大学学报（医学版）,2026,47(10):1310-1317.

HU Xiaoli,LEI Ji,LI Jiahao,et al.Tectorigenin alleviates doxorubicin‐induced cardiotoxicity through activating SIRT1/FOXO1 signaling pathway[J].Medical Journal of Wuhan University,2026,47(10):1310-1317.
胡小丽,雷霁,李佳昊等.鸢尾苷元通过激活SIRT1/FOXO1信号通路减轻阿霉素心肌毒性[J].武汉大学学报（医学版）,2026,47(10):1310-1317. DOI： 10.14188/j.1671-8852.2025.1181.

HU Xiaoli,LEI Ji,LI Jiahao,et al.Tectorigenin alleviates doxorubicin‐induced cardiotoxicity through activating SIRT1/FOXO1 signaling pathway[J].Medical Journal of Wuhan University,2026,47(10):1310-1317. DOI： 10.14188/j.1671-8852.2025.1181.

摘要

目的

探讨鸢尾苷元（TEC）对阿霉素（DOX）诱导的心脏毒性的保护作用及其潜在分子机制。

方法

采用单次腹腔注射阿霉素（15 mg·kg

-1

）构建心肌损伤模型。将小鼠随机分为4组（每组12只）：生理盐水+溶剂组、生理盐水+TEC组、DOX+溶剂组、DOX+TEC组。造模后第2天开始给予小鼠TEC灌胃（剂量为40 mg·kg

-1

·d

-1

），连续7 d，对照组给予等体积溶剂灌胃。模型建立后行心脏超声检查并采集样本；测量小鼠一般情况及心脏大体指标；HE染色法观察心肌细胞形态学变化；提取小鼠心脏组织和血清进行病理及生化分析。使用试剂盒检测心肌损伤标志物水平及半胱氨酸蛋白酶3（caspase‐3）活性；DHE染色和4‐HNE染色评估心肌氧化应激水平；RT‐PCR检测相关基因的mRNA表达；通过TUNEL免疫荧光染色评估心肌细胞凋亡情况；Western Blot检测sirtuin 1（SIRT1）、乙酰化叉头框蛋白O1（AC‐FOXO1）等蛋白表达水平。

结果

DOX导致小鼠的心脏功能显著下降（

0.05），而经过TEC处理的小鼠心功能有显著改善（

0.05）。与生理盐水对照组小鼠相比，DOX处理后小鼠的体质量和心脏重量均降低，心肌损伤的标志物水平显著升高（

0.05）；TEC处理明显降低了心肌损伤标志物水平，改善了小鼠的整体健康状况（

0.05）。TEC显著降低了DOX处理小鼠的心脏氧化应激水平（

0.05）。与生理盐水对照组小鼠相比，DOX处理使小鼠心脏caspase‐3活性升高（

0.05），TUNEL阳性细胞的数量和占比显著增加（

0.05），而TEC处理后上述指标较DOX组显著降低（

0.05）。机制上，TEC可上调心脏SIRT1蛋白水平，促进FOXO1蛋白去乙酰化并激活FOXO1，从而促进下游抗氧化基因表达。

结论

TEC通过靶向SIRT1‐FOXO1通路，改善DOX诱导的心功能障碍、心肌损伤、心脏氧化应激和心肌细胞凋亡。

Abstract

Objective

To explore the protective role and underlying molecular mechanism of tectorigenin (TEC) against doxorubicin (DOX)⁃induced cardiotoxicity.

Methods

A doxorubicin⁃induced cardiomyopathy model was established by a single intraperitoneal injection of DOX (15 mg·kg⁻¹) in mice. Mice were randomly divided into four groups (

=12 each): saline+vehicle

saline+TEC

DOX+vehicle

and DOX+TEC. TEC (40 mg·kg⁻¹·d⁻¹) was administered by intragastric gavage for 7 consecutive days starting on day 2 after model establishment; control groups received an equivalent volume of vehicle. Cardiac function was assessed by echocardiography

and samples were subsequently collected. General condition and gross cardiac parameters were evaluated. Hematoxylin⁃eosin (HE) staining was used to observe morphological changes in cardiomyocytes. Heart tissue and serum were harvested for pathological and biochemical analyses. Myocardial injury markers and caspase⁃3 activity were measured using commercial assay kits. D

HE and 4⁃HNE staining were used to assess myocardial oxidative stress. RT⁃PCR was used to detect mRNA levels of related genes. TUNEL staining was used to evaluate cardiomyocyte apoptosis

and Western Blot was used to detect protein expression of sirtuin 1 (SIRT1)

acetylated forkhead box protein O1 (AC⁃FOXO1)

and other related proteins.

Results

DOX significantly impaired cardiac function (

0.05)

whereas TEC treatment markedly improved cardiac function (

0.05). Compared with the control group

DOX led to decreased body mass and heart weight

and increased levels of myocardial injury markers (

0.05); TEC administration significantly reduced myocardial injury marker levels and improved the general condition of mice (

0.05). TEC also attenuated cardiac oxidative stress in DOX⁃treated mice (

0.05). Compared with controls

DOX increased cardiac caspase⁃3 activity (

0.05) and the proportion of TUNEL⁃positive cells (

0.05)

while TEC treatment reduced caspase⁃3 activity and the TUNEL⁃positive cell rate (

0.05). Mechanistically

TEC upregulated cardiac SIRT1 protein expression

promoted FOXO1 deacetylation

and activated FOXO1 to induce downstream antioxidant gene expression.

Conclusion

TEC attenuates doxorubicin⁃induced cardiac dysfunction

myocardial injury

oxidative stress

and cardiomyocyte apoptosis via the SIRT1⁃FOXO1 signaling pathway.

关键词

Keywords

references

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