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

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。

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

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.