中国医科大学学报2025，Vol.54Issue(7)：619-625,7.DOI:10.12007/j.issn.0258-4646.2025.07.008
米诺环素调节HIF-1α/BNIP3信号通路对慢性心力衰竭大鼠心肌细胞损伤的影响
Minocycline alleviates myocardial cell damage in chronic heart failure rats by regulating the HIF-1α/BNIP3 signaling pathway
摘要
Abstract
Objective To investigate the impact of minocycline(MC)on myocardial cell damage in rats with chronic heart failure(CHF)by regulating the hypoxia-inducible factor 1α(HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein(BNIP3).Methods All rats were randomly divided into Sham,CHF,positive drug(LP),low dose MC,high dose MC(HMC),and HMC+HIF-1α activator(DMOG)groups.Cardiac function was detected using echocardiography.HE staining,transmission electron microscopy,and TUNEL assay were used to evaluate myocardial pathology and apoptosis.Enzyme-linked immunosorbent assay was applied to quantify tumor necrosis factor α(TNF-α),interleukin-1β,superoxide dismutase(SOD),and malondialdehyde(MDA).Quantitative real-time PCR was used to detect the mRNA levels of Bcl-2 and Bcl-2-related X protein(Bax),while Western blotting was applied to detect the expres-sion of HIF-1α,BNIP3,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)proteins.Results Compared to rats in the sham group,rats from the CHF group exhibited increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),cell apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,and LC3Ⅱ/Ⅰwith decreased left ventricular ejection fraction(LVEF),left ventricular shortening fraction(LVFS),SOD,and Bcl-2 levels(P<0.05).Compared with CHF group,rats from LP group,LMC group and HMC group exhibited decreased levels of LVEDD,LVESD,apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,LC3Ⅱ/Ⅰ,and increased levels of LVEF,LVFS,SOD and Bcl-2(P<0.05).DMOG attenuated the protective effect of high-dose MC on myocardial cell damage in rats of the CHF group(P<0.05).Conclusion MC improves myocardial cell damage in rats of CHF group by inhibiting the HIF-1α/BNIP3 signaling pathway.关键词
米诺环素/HIF-1α/BNIP3信号通路/慢性心力衰竭/心肌细胞Key words
minocycline/HIF-1α/BNIP3 signaling pathway/chronic heart failure/myocardial cell分类
医药卫生引用本文复制引用
姜帆,周泓屹,王飞跃,孙源,吴广明..米诺环素调节HIF-1α/BNIP3信号通路对慢性心力衰竭大鼠心肌细胞损伤的影响[J].中国医科大学学报,2025,54(7):619-625,7.基金项目
首都卫生发展全科医学与社区卫生科研专项(2023-2Y-014) （2023-2Y-014）
