文献类型：期刊文献

英文题名：Astragaloside IV alleviates radiation-induced heart disease by regulating energy metabolism

作者：Li, Qiyang[1];Zhang, Shangzu[2];Li, Yangyang[1];Yao, Ning[1];Feng, Yuye[1];Yang, Gengqiang[1];Wang, Yutong[1];Dai, Sichao[1];Cheng, Shuai[1];Zhou, Ting[1];Wang, Xin[1];Zhang, Liying[1,3]

第一作者：Li, Qiyang

通信作者：Zhang, LY[1]

机构：[1]Gansu Univ Chinese Med, Prov Key Lab Mol Med & Prevent Res Major Dis, Lanzhou 730000, Peoples R China;[2]Hubei Univ Chinese Med, Wuhan 430065, Peoples R China;[3]Gansu Inst Cardiovasc Dis, Lanzhou 730050, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：146

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-105012303948);WOS:【SCI-EXPANDED(收录号:WOS:001551875100001)】；

基金：This project was supported by the National Natural Science Foundation of China (NSFC) (No. 82260882) ; Gansu Basic Research Innovation Group (25JRRA247) ; Open Foundation of Key Laboratory of Dunhuang Medicine and Transformation (DHYX23-09) .

语种：英文

外文关键词：Radiation-induced heart disease; Metabolomics; HIF-1 alpha; AQPs; AS-IV; Radiotherapy

摘要：Background: Radiation-induced heart disease (RIHD) has emerged as a critical complication compromising the long-term survival of cancer patients undergoing radiotherapy. Although targeting myocardial energy metabolism is a promising therapeutic strategy for cardiovascular diseases, the molecular mechanisms underlying ionizing radiation-induced cardiomyocyte metabolic dysregulation and subsequent cardiac injury remain unclear. Purpose: This study aims to explore the mechanism by which Astragaloside IV (AS-IV) alleviates RIHD through the regulation of energy metabolism. Methods: This study established mouse and cellular models of radiation-induced heart injury to investigate the effects of X-ray radiation on energy metabolism in the hearts of C57BL/6 mice and in cardiomyocyte cell lines (AC16 and H9C2). By integrating untargeted metabolomics with experimental validation, we elucidated the pharmacological effects and molecular mechanisms of the HIF-1 alpha inhibitor (PX-478) and AS-IV intervention in mouse heart tissue and cardiomyocytes. Results: In vitro experiments demonstrated that X-rays at doses of 6 Gy and above induced damage and abnormal energy metabolism in H9C2 and AC16 cardiomyocytes at 24, 48, and 72 h, respectively. These abnormalities were primarily characterized by inhibited cell proliferation, increased apoptosis, decreased ATP content, and elevated lactate and lipid accumulation. These phenomena may be associated with the abnormal activation of the HIF-1 alpha/PPAR gamma signaling pathway. Additionally, AS-IV effectively mitigated radiation-induced cardiomyocyte injury by regulating HIF-1 alpha/PPAR gamma-mediated glycolysis and triglyceride synthesis metabolism, as well as by alleviating mitochondrial damage. Conclusion: Abnormal activation of the HIF-1 alpha/PPAR gamma axis may represent a potential mechanism underlying Xray-induced abnormalities in myocardial energy metabolism and cellular damage. Furthermore, AS-IV has the potential to alleviate radiocardiac injury by modulating energy metabolism and restoring mitochondrial function.