中国实验动物学报2024,Vol.32Issue(5):557-565,9.DOI:10.3969/j.issn.1005-4847.2024.05.002
基于斑马鱼模型探讨八宝丹对阿霉素所致心肌损伤的保护作用及机制
Protective effect and mechanism of Ba Bao Dan on doxorubicin-induced myocardial injury in a zebrafish model
摘要
Abstract
Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P<0.05),decreased malondialdehyde concentration(P<0.05),and enhanced the activities of superoxide dismutase and catalase(P<0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P<0.05),and promoted the expression of gpx4a(P<0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.关键词
八宝丹/阿霉素/斑马鱼/心肌损伤/脂质过氧化/铁死亡Key words
Ba Bao Dan/doxorubicin/zebrafish/myocardial injury/lipid peroxidation/ferroptosis分类
生物科学引用本文复制引用
李宪美,曾来凤,黄彬,余岚心,林久茂..基于斑马鱼模型探讨八宝丹对阿霉素所致心肌损伤的保护作用及机制[J].中国实验动物学报,2024,32(5):557-565,9.基金项目
国家自然科学基金(82204925),福建中医药大学校管课题(X2020010-重点),福建中医药大学人才专项(X2020013-人才).Funded by National Natural Science Foundation of China(82204925),School Management Project of Fujian University of Traditional Chinese Medicine(X2020010-Key),Talent Program of Fujian University of Traditional Chinese Medicine(X2020013-Talent). (82204925)