胞外信号调节激酶1/2通路在阿霉素引起的心肌细胞损伤中的作用  

Role of ERK1/2 pathway in doxorubicin-induced cardiomyocyte injury

作　　者：张莉莉[1,2] 赖东平 王秀玉[4] 郑东诞[5] 郭润民[4] 沈宁[4] 陈培熹[4] 冯鉴强[4] 

机构地区：[1]广东省医学科学院广东省人民医院 [2]广东省老年医学研究所综合科,广东广州510080 [3]江西省龙南县妇幼保健院内科,江西龙南341700 [4]中山大学中山医学院生理学教研室,广东广州510080 [5]中山大学附属第一医院黄埔院区心血管内科,广东广州510080

出　　处：《中国药理学通报》2012年第7期961-966,共6页Chinese Pharmacological Bulletin

基　　金：广东省科技计划项目(No 2011B080701051;2010B080701105;2010B080701035;2010B080701015)

摘　　要：目的探讨胞外信号调节激酶1/2(ERK 1/2)通路在阿霉素(doxorubicin,DOX)引起的心肌细胞损伤中的作用。方法应用DOX处理H9c2心肌细胞建立细胞损伤的体外模型,在DOX处理前应用ERK 1/2抑制剂PD98059抑制ERK 1/2的活化;检测细胞存活率、ERK 1/2的活化、胞内活性氧(ROS)水平、线粒体膜电位(MMP)以及胱硫醚γ-裂解酶(CSE,为内源性硫化氢的合成酶)的表达。结果 5μmol·L-1DOX处理H9c2心肌细胞1～6 h,呈时间依赖性地促进ERK1/2的活化;5μmol·L-1DOX对心肌细胞具有明显的损伤作用,表现为细胞存活率下降、ROS水平升高、MMP丢失及CSE表达降低;在DOX处理H9c2心肌细胞前30min,应用ERK1/2抑制剂10μmol·L-1PD-98059预处理能明显拮抗DOX对心肌细胞的损伤作用,使ROS水平降低,细胞存活率MMP和CSE表达水平均升高。结论 ERK1/2通路参与DOX对H9c2心肌细胞的损伤作用。Aim To investigate the role of extracellular signal-regulated kinases 1/2（ERK1/2） pathway in doxorubicin（DOX）-induced injury in H9c2 cardiac cells（H9c2 cells）.Methods H9c2 cells were treated with DOX to establish a model of cellular injury.PD-98059 was applied before exposure to DOX to inhibit ERK1/2 pathway.Cell viability,activation of ERK1/2,intracellular reactive oxygen species（ROS）,mitochondrial membrane potential（MMP） and cystathionine-γ-lyase（CSE,a synthase of endogenous hydrogen sulfide） expression were tested.Results Exposure of H9c2 cells to 5 μmol·L-1 DOX for 1 to 6 h time-dependently induced the activation of ERK1/2.DOX at 5 μmol·L-1 had a damage effect on H9c2 cells,evidenced by decreases in cell viability,MMP and expression of CSE,and an increase in intracellular ROS level.Pretreatment with PD-98059 at 10 μmol·L-1 for 30 min before exposure of H9c2 cells to DOX significantly blocked DOX-induced cell injury,leading to increases in cell viability,MMP and CSE expression,and a decrease in ROS level.Conclusion ERK1/2 pathway is involved in H9c2 cell injury induced by DOX.

关 键 词：阿霉素 心肌毒性 H9C2心肌细胞 氧自由基 线粒体膜电位 胞外信号调节激酶1/2 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R345.57[医药卫生—基础医学]