整合素连接激酶对阿霉素诱导心肌细胞凋亡的影响

目的探讨高表达整合素连接激酶(ILK)对阿霉素(DOX)诱导心肌细胞凋亡的影响及其机制。方法体外培养乳鼠心肌细胞,分为正常对照组(转染Ad-GFP)、阿霉素损伤组(转染Ad-GFP+DOX)、ILK转染组(转染Ad-ILK+DOX)采用原位末端缺口标记法(TUNEL)检测心肌细胞凋亡率;real-time PCR检测心肌细胞Fas、FasL、Bax、Bel-2 mRNA的表达水平。结果与对照组相比,阿霉素损伤组心肌细胞凋亡率明显升高(P<0.01),Fas、FasL、Bax mRNA的表达水平明显增高(P<0.01),Bcl-2 mRNA的表达明显降低(P<0 01);与阿霉素损伤组相比,ILK转染组心肌细胞凋亡率显著降低(P<0.05),Fas、FasL、Bax mRNA的表达水平明显(均P<0.01),Bcl-2 mRNA的表达明显增加(P<0.05)。结论高表达ILK通过抑制心肌细胞Fas、FasL、Bax mRNA的表达、上调Bcl-2 mRNA的表达而抑制阿霉素诱导的心肌细胞凋亡。

Effects of integrin-linked kinase on apoptosis induced by doxorubicin in cardiomyocytes

Objective To explore the effects of integrin - linked kinase(ILK)on apoptosisinduced by doxorubicin(DOX) in cardiomyocytes and to investigate its possible mechanism.Methods Cultured neonatal rat cardiomyocytes were randomly divided into three groups;control group,GFP + DOX group and ILK + DOX group.The apoptosis rate of myocardial cells was determined by terminal deoxynucleotidyl transferase - mediated dUTP - biotin nick end labeling(TUNEL).Expression of several apoptosis -related genes,including Fas,FasL,Bax and Bcl -2 in cardiomyocytes was examined by fluorescent quantitative real - time PCR.Results The ratio of apoptotic cardiomyocytes in GFP + DOX group was significantly higher than that in control group(P<0.01),but in ILK + DOX group,it was lower than that in GFP + DOX group(P<0.05).Compared with control group,the mRNA expression of Fas,FasL and Bax was higher(P<0.01),and the mRNA expression of Bcl - 2 was lower than that in control group(P<0.01).In ILK + DOX group,the mRNA expression of Fas, FasL and Bax was lower than that in GFP + DOX group(P<0.05),and the mRNA expression of Bcl - 2 was higher(P<0.05).Conclusion Over - expression of ILK inhibits DOX - induced apoptosis in cardiomyocytes by up - regulating the expression of Bcl - 2 and inhibiting the expression of Fas, FasL and Bax.