衰老心肌中热休克因子1的表达与线粒体损伤的关系

目的 探讨衰老心肌中热休克因子（heat shock factor 1，HSF1）的表达与线粒体损伤的相关性。方法 选用4月龄、24月龄的C57 BL/6小鼠作为年轻鼠和衰老鼠，运用透射电镜观察心肌组织中线粒体形态学的改变。用ATP检测试剂盒检测衰老心肌及H9C2心肌细胞中ATP的含量，利用活性氧（reactive oxygen species，ROS）检测试剂盒分析衰老心肌及H9C2心肌细胞中ROS的变化，采用JC-1染色法检测心肌细胞膜电位的改变，利用Western blotting法检测心脏组织及心肌细胞中HSF1的表达。结果 与年轻小鼠相比，衰老小鼠心肌组织中线粒体的形态异常；衰老小鼠心肌组织中ATP含量下降（1.253±0.059 vs 0.479±0.122，P=0.012），ROS的含量上升（10.853±0.096 vs 1.550±0.233，P=0.025）；衰老小鼠心肌组织中HSF1的表达增高（0.980±0.112 vs 1.979±0.175，P=0.013）；衰老心肌中HSF1的表达与ATP的浓度呈负相关（r=-0.977，P=0.005），与ROS的含量呈正相关（r=0.934，P=0.020）；过氧化氢（H₂O₂）刺激后H9C2心肌细胞线粒体膜电位下降，ATP含量下降，ROS的含量上升，HSF1表达升高（P<0.05）。结论 衰老的心肌中损伤的线粒体功能与HSF1的表达呈负相关。

Relationship between the expression of heat shock factor 1 and mitochondrial damage in aging myocardium

Objective To explore the relationship between mitochondrial damage and the expression of heat shock factor 1 (HSF1) in aging myocardium.Methods Four-month-old and 24-month-old C57BL/6 mice were used as the young and aging mices. The changes of the morphology in mitochondria were observed by transmission electron microscopy in the myocardial tissue.The concentration of ATP and the production of reactive oxygen species (ROS) in aging myocardium and H9C2 cells were detected by related kits.JC-1 was used to detect the change of membrane potential in H9C2 cells.The expression of HSF1 was detected by Western blotting. Results In the aging myocardium, the morphology of mitochondria was changed and the concentration of ATP was decreased(1.253±0.059 vs 0.479±0.122, P=0.012), the production of ROS was increased(10.853±0.096 vs 1.550±0.233, P=0.025), and the expression of HSF1 was also increased in the aging myocardium (0.980±0.112 vs 1.979±0.175, P=0.013). The expression of HSF1 in aging myocardium was negatively correlated with the content of ATP (r=-0.977, P=0.005) and positively correlated with the content of ROS (r=0.934, P=0.020). After treated with H₂O₂, the mitochondrial membrane potential of cardiomyocytes decreased, the content of ATP decreased and the content of ROS increased,the expression of HSF1 was increased in the cardiomyocytes(P<0.05).Conclusion During the aging process,the mitochondria is damaged and the dysfunction of mitochondria was negatively correlated with the expression of HSF1 in aging myocardium.