阿霉素中毒心肌细胞钙离子调节功能的变化

Effects of Doxorubicin(DOX) on the function of the Myocardial intracellular Calcium handling

本文采用Fura-2/AM荧光标记同位素^(45)Ca^(2+)负载示踪法测定了心肌细胞内钙浓度及肌浆网摄钙功能,探讨了阿霉素对心肌细胞内钙调节功能的影响,同时还观察了维拉帕米预处理10min后,阿霉素对心肌细胞内钙浓度及钙调节功能的影响.结果显示,阿霉素作用早期(10min)能够增加心肌细胞外钙的快相内流,使心肌细胞内游离钙浓度增高,肌浆网摄钙量也有轻度增加,阿霉素作用60min后,与对照组相比细胞内^(45)Ca^(2+)总量增加,而肌浆网对^(45)Ca^(2+)的摄取明显减低,细胞浆内游离钙浓度明显升高.维拉帕米预处理组,维拉帕米部分阻断了阿霉素对细胞内钙的调节作用.结果提示,阿霉素通过增加心肌细胞钙内流速度和抑制肌浆网摄钙量,导致心肌细胞钙过负荷,进而影响心肌细胞的收缩舒张功能.

To explore the effects of DOX on the myocardial intracellular calcium handling, the intracellular concentrations of free calcium and the sarcoplasmic reticulum(SR) Ca2+uptake function were determined using the fura-2/AM fluorescence and the isotope 45Ca2+loading, and the effect of DOX on the intracellular calcium concentrations and the calcium handling function were observed after 10 min of pretreatment with calcium antagonist. The results indicated that DOX could increase the rapid influ of myocardial extracellular calcium, raise the intracellular concentrations of free calcium and enhance the SR Ca2+uptake at the early stage (10 min). However after 60 min of treatment with DOX, the SR 45Ca2+ uptake was decreased whereas the cytosolic concentration of free calcium was increased significantly compared with the control group. In the Verapamil pretreatment group, Verapamil hindered the regulatory effect of DOX on the intracellular calcium. It suggested that DOX could introduce the intracellular calcium overloading by increasing the rate of 45Ca2+ influ and decreasing the amount of SR 45Ca2+uptake and further control systolic and diastolic function of the myocardial cells.