| 雷贝拉唑对阿霉素诱导心肌细胞损伤的保护作用及机制研究 |
| 投稿时间：2025-07-30 修订日期：2025-08-21 点此下载全文 |
| 引用本文：赵淑红,黄丹,王世瑛,马振国.雷贝拉唑对阿霉素诱导心肌细胞损伤的保护作用及机制研究[J].医学研究杂志,2026,55(1):36-41 |
| DOI：
10.11969/j.issn.1673-548X.2026.01.008 |
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| 基金项目:国家自然科学基金青年科学基金资助项目(81700254)；湖北省青年拔尖人才项目 |
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| 中文摘要:目的 研究雷贝拉唑(rabeprazole,Rab)对阿霉素(doxorubicin,DOX)诱导的心脏毒性的保护作用及潜在机制。方法 体外构建DOX(1μmol/L)诱导的H9C2心肌细胞损伤模型,用不同浓度的Rab(1、5、10、20和50μmol/L)进行干预。通过CCK-8法检测细胞活力,确定Rab最佳干预浓度为10μmol/L,并用于后续实验。将H9C2心肌细胞随机分为4组,即Ctrl组、Rab组、DOX组和DOX+Rab组。通过检测乳酸脱氢酶(lactate dehydrogenase,LDH)及肌酸激酶同工酶MB(creatine kinase-MB,CK-MB)水平评估心肌细胞损伤情况；Western blot法检测心肌细胞凋亡水平；DCFH-DA探针法、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)试剂盒检测氧化应激水平；JC-1染色与三磷酸腺苷(adenosine triphosphate,ATP)含量测定分析线粒体功能变化；Western blot法检测Kelch样ECH相关蛋白1/核因子E2相关因子2/血红素氧合酶-1(kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1,Keap1-Nrf2/HO-1)信号通路蛋白表达改变情况。结果 与Ctrl组比较,DOX处理显著降低心肌细胞活力,升高LDH和CK-MB释放水平,并促进细胞凋亡(P＜0.05)。DOX显著增加活性氧(reactive oxygen species,ROS)和MDA水平,抑制抗氧化酶GSH-Px活性(P＜0.05)。同时,DOX处理导致线粒体膜电位下降及ATP合成减少(P＜0.05)。Rab干预可明显减轻DOX诱导的心肌细胞损伤,提高抗氧化水平,改善线粒体功能障碍(P＜0.05)。机制上,Rab能够上调核内Nrf2蛋白表达,促进Nrf2核转位,并增强其下游抗氧化基因的表达(P＜0.05)。结论 Rab抑制细胞凋亡和氧化应激,减轻DOX引起的心肌细胞毒性,可能通过调控Keap1-Nrf2/HO-1通路发挥作用。 |
| 中文关键词:雷贝拉唑 阿霉素 凋亡 氧化应激 线粒体 |
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| Protective Effects and Mechanisms of Rabeprazole Against Doxorubicin-Induced Cardiomyocyte Injury. |
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| Abstract:Objective To investigate the protective effects and underlying mechanisms of rabeprazole (Rab) against doxorubicin (DOX)-induced cardiotoxicity. Methods An in vitro model of DOX-induced injury was established in H9C2 cardiomyocytes using 1μmol/L DOX, and cells were treated with various concentrations of Rab (1,5, 10,20 and 50μmol/L). Cell viability was assessed using the CCK-8 assay to determine the optimal concentration of Rab (10μmol/L) for subsequent experiments. H9C2 cardiomyocytes were randomly divided into four groups:Ctrl group, Rab group, DOX group and DOX+Rab group. Myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels. Apoptosis was assessed by Western blot analysis. Oxidative stress was evaluated using the DCFH-DA probe and assay kits for malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). Mitochondrial function was analyzed by JC-1staining and measurement of adenosine triphosphate (ATP) levels. Protein expression changes in the kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Keap1-Nrf2/HO-1) signaling pathway were detected by Western blot. Results Compared with the Ctrl group, DOX treatment significantly reduced cell viability, increased the release of LDH and CK-MB, and promoted apoptosis (P<0.05). DOX markedly elevated levels of reactive oxygen species (ROS) and MDA, and suppressed GSH-Px activity (P<0.05). In addition, DOX caused a decrease in mitochondrial membrane potential and ATP production (P<0.05). Rab treatment alleviated DOX-induced myocardial injury, improved antioxidant capacity, and restored mitochondrial function (P<0.05). Mechanistically, Rab enhanced nuclear Nrf2 expression, promoted its nuclear translocation, and upregulated downstream antioxidant genes (P<0.05). Conclusion Rab alleviates DOX-induced cardiotoxicity by inhibiting apoptosis and oxidative stress, potentially through regulation of the Keap1-Nrf2/HO-1signaling pathway. |
| keywords:Rabeprazole Doxorubicin Apoptosis Oxidative stress Mitochondria |
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