摘要
目的研究阿霉素对心脏结构功能的影响以及此过程中部分相关信号通路的变化。方法用20只SD大鼠分为两组:阿霉素组(10只)和正常组(10只),观察阿霉素对心脏结构及功能改变,心肌细胞凋亡以及p-AKT与p-ERK1/2的蛋白水平。结果阿霉素注射11周后造成肌纤维排列紊乱,肌纤维丢失及肌浆空泡化,心脏功能尤其是收缩功能下降(FS与CO比较,P<0.01),心肌细胞凋亡增加,p-AKT与p-ERK1/2的蛋白水平较正常明显下降。结论阿霉素能明显造成心脏结构及功能的损伤,心肌细胞凋亡,PI3K/AKT与ERK1/2两条信号通路的变化可能参与到阿霉素的心脏毒性过程中。
Objective To investigate the role of PI3K/AKT and ERK1/2 signaling pathways in the process of cardiomyopathy induced by doxorubicin （DOX）. Methods Twenty SD rats were divided into two groups ： DOX group （ 10 rats that were injected through caudal vein with 2.5 mg/kg DOX, once a week, for 6 weeks） and control group （10 rats）. At 56th week after the end of DOX injection, the structural changes and functional damage were examined, and the apoptosis rate of cardiomyocytes and the expression levels of p-AKT and p-ERK1/2 were determined. Results Eleven weeks after the DOX injection, the myocardial pathological changes were mainly myofibrillar loss and cytoplasmic vacuolization. DOX could induce compensated heart function （ the value of FS% was 34, P 〈 0.01 as compared with control group）. DOX caused cardiac cell apop- tosis and the apoptosis ratio was 28.4% （P 〈0.01, as compared with control group）. The expression of Bcl-2 increased to 126% （ P 〉 0.05 ） and Bax to 338 % （ P 〈 0.05 ） of control level. In DOX group, phosphorylation of Akt was reduced to 12% （P 〈0.05 ） and that of ERK1/2 was reduced to 24% （P 〈0.05 ） of control level. Conclusion DOX can induce the damage of cardiac function and the apoptosis of cardiomyocytes, in which the PI3K/AKT and ERK1/2 signaling pathways may play important roles.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第11期1071-1074,共4页
Journal of Third Military Medical University
关键词
阿霉素
心肌病
心脏毒性
细胞凋亡
信号通路
doxorubicin
cardiomyopathy
cardiotoxicity
apoptosis
signaling pathway
