整合素连接激酶对阿霉素诱导心肌细胞凋亡的影响  

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

作　　者：孙静娴[1] 白剑[2] 王丙剑[1] 毛雅晶[2] 徐标[1] 

机构地区：[1]南京医科大学鼓楼临床医学院心脏科,江苏南京210008 [2]南京大学医学院附属鼓楼医院心脏科,江苏南京210008

出　　处：《实用临床医药杂志》2011年第7期16-20,共5页Journal of Clinical Medicine in Practice

基　　金：国家自然科学基金项目(81070195)

摘　　要：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。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（P0.01）,but in ILK ＋ DOX group,it was lower than that in GFP ＋ DOX group（P0.05）.Compared with control group,the mRNA expression of Fas,FasL and Bax was higher（P0.01）,and the mRNA expression of Bcl - 2 was lower than that in control group（P0.01）.In ILK ＋ DOX group,the mRNA expression of Fas, FasL and Bax was lower than that in GFP ＋ DOX group（P0.05）,and the mRNA expression of Bcl - 2 was higher（P0.05）.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.

关 键 词：整合素连接激酶 阿霉素 心肌细胞 凋亡 

分 类 号：R541.9[医药卫生—心血管疾病]