金银花提取物对阿霉素诱导的小鼠心肌损伤的保护作用及其机制

夏士程; 韦慧芳; 洪维灿; 张钰明; 尹菲玚; 张贻欣; 张淋淋; 高琴; 叶红伟

doi:10.12122/j.issn.1673-4254.2025.12.01

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (12) : 2527 -2540. DOI: 10.12122/j.issn.1673-4254.2025.12.01

金银花提取物对阿霉素诱导的小鼠心肌损伤的保护作用及其机制

夏士程 ¹^,³ ,
韦慧芳 ¹^,³ ,
洪维灿 ¹^,³ ,
张钰明 ²^,³ ,
尹菲玚 ¹^,³ ,
张贻欣 ¹^,³ ,
张淋淋 ²^,³ ,
高琴 ²^,³ ,
叶红伟 ²^,³

作者信息 +

Protective effect of Lonicerae Japonicae Flos extract against doxorubicin-induced myocardial injury in mice and the possible mechanisms

Shicheng XIA ¹^,³ ,
Huifang WEI ¹^,³ ,
Weican HONG ¹^,³ ,
Yuming ZHANG ²^,³ ,
Feiyang YIN ¹^,³ ,
Yixin ZHANG ¹^,³ ,
Linlin ZHANG ²^,³ ,
Qin GAO ²^,³ ,
Hongwei YE ²^,³

Author information +

文章历史 +

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摘要

目的探讨金银花（LJF）对阿霉素（DOX）诱导的心肌损伤的保护作用及其机制。方法通过网络药理学、生物信息学分析与分子对接技术预测核心靶点，并通过动物实验加以验证。动物实验中，检测DOX诱导的心肌损伤及不同剂量LJF提取物治疗后小鼠心功能、心肌酶学、心肌组织形态、炎症因子及相关蛋白表达的变化。结果网络药理学筛选出LJF的10个核心活性成分可与AKT、EGFR、GSK3β良好结合。动物实验结果显示，与假手术组相比，DOX组小鼠心输出量、每搏输出量、左室射血分数及左室短轴缩短率显著降低，血清CK-MB、LDH水平升高，心肌IL-18、IL-1β含量增加；HE染色示心肌结构损伤；心肌组织NLRP3、caspase-1、GSDMD及GSDMD-N蛋白表达上调，EGFR蛋白表达下调，p-AKT、p-GSK3β蛋白水平降低。与DOX组相比，LJF治疗后小鼠心功能明显改善，心肌组织中IL-18、IL-1β水平降低，NLRP3、caspase-1、GSDMD及GSDMD-N蛋白表达下调， EGFR蛋白水平上调，p-AKT、p-GSK3β蛋白磷酸化水平提高。结论金银花可能通过靶向作用于EGFR、AKT、GSK3β调控ErbB信号通路，抑制心肌组织炎症反应与细胞焦亡，从而减轻阿霉素诱导的心肌损伤。

Abstract

Objective To evaluate the protective effect of Lonicerae Japonicae Flos (LJF) extract against doxorubicin (DOX)-induced cardiotoxicity (DIC) and explore the possible mechanisms. Methods Network pharmacology, bioinformatics analysis and molecular docking were used to predict the targets of the core components of LJF. In a mouse model of DOX-induced myocardial injury, the protective effects of different doses of LJF extract were evaluated and the underlying mechanisms were explored by detecting the changes in mouse myocardial functions, myocardial enzymes, myocardial pathologies, and the expressions of inflammatory factors and pyroptosis-related proteins. Results The 10 core ingredients of LJF showed strong binding to AKT, EGFR, and GSK3β. In the animal experiment, the DOX-treated mice, compared with the sham-treated mice, had significantly decreased cardiac output, stroke volume, left ventricular ejection fraction, left ventricular fraction shorting, elevated serum levels of CK-MB and LDH, increased myocardial expressions of IL-18 and IL-1β, obvious myocardial damage, increased expression levels of NLRP3, caspase-1, GSDMD and GSDMD-N, and reduced expressions of EGFR, p-AKT and p-GSK3β proteins in the myocardial tissues. LJF treatment obviously improved myocardial function, decreased myocardial expressions of IL-18, IL-1β, NLRP3, caspase-1, GSDMD and GSDMD-N proteins, and increased the expressions EGFR, p-AKT and p-GSK3β proteins in DOX-treated mice. Conclusion LJF extract alleviates DOX-induced myocardial injury in mice possibly by reducing myocardial inflammation and pyroptosis via targeting EGFR, AKT and GSK3β to regulate the ErbB signaling pathway.