凋亡信号调节激酶1在扩张型心肌病大鼠中的表达及其与左心室射血分数的相关性

摘要

目的 探讨凋亡信号调节激酶1(ASK1)在多柔比星诱导的扩张型心肌病(DCM)模型大鼠左心室心肌的表达变化及其与左心室射血分数(LVEF)的相关性.方法 选择SPF级Wistar大鼠120只,按随机数字表法分为对照组(n=15)和模型组(n=105).模型组大鼠用多柔比星经腹腔注射,对照组用9 g/L盐水腹腔注射,每周3次,间隔2周后再重复1周,共6次,8周末确定DCM大鼠模型.分别于第8周末、12周末抽取模型组及对照组大鼠检测其LVEF,并应用凋亡细胞原位标志与半定量分析法及Western blot技术分别检测其心肌凋亡细胞阳性指数(AI)及心肌ASK1.结果 对照组、8周末模型组、12周末模型组AI分别为0.53±0.27、16.13±1.72、19.54 ±2.24,8周末模型组、12周末模型组明显高于对照组,3组间比较差异有统计学意义(F=18.98,P＜0.05).对照组、8周末模型组和12周末模型组大鼠心室肌ASK1相对表达量分别为0.169 ±0.010、0.649 ±0.071、0.781±0.077,3组间比较差异有统计学意义(F=27.72,P＜0.01).对照组、8周末模型组及12周末模型组LVEF(％)分别为75.41 ±2.02、53.25±3.74、39.21±6.13,3组间比较差异有统计学意义(F=154.87,P＜0.01).12周末模型组大鼠心肌ASK1相对表达量与LVEF呈负相关(r=-0.86,P＜0.01).结论 DCM大鼠心肌ASK1的表达明显增多.ASK1介导的凋亡信号调节途径可能参与DCM的病理生理过程.%Objective To observe the changes of apoptosis signal-regulating kinase 1 (ASK1) expression in left ventricular myocardium of the dilated cardiomyopathy (DCM) rats induced by adriamycin and its correlation with left ventricular ejection fraction (LVEF).Methods One hundred and twenty SPF Wistar rats were divided into 2 groups as follows:control group (n =15),model group(n =105).Adriamycin was administered in the model group by intraperitoneal injection for 3 times in a week and repeated with a two-week interval for 6 times,while 9 g/L saline were administered in the control group in the same pattern,thus DCM rats model were constructed by the end of the 8th week.Both the model group and control group rats were drawn out and their LVEF were tested by the end of the 8th week and 12th week.Apoptosis index (AI) and the ASK1 in myocardium were tested respectively by apoptotic cells situ labeling,semi-quantitative analysis and Western blot.Results The AI of the control group,the 8th weekend model group and the 12th weekend model group were 0.53 ±0.27,16.13 ± 1.72,19.54 ±2.24.The AI of the 8th and the 12th weekend model groups were obviously higher than that in the control group.Comparing the differences among the 3 groups were statistically significant (F =18.98,P ＜ 0.05).The relative ASK1 expressions in ventricular myocardium of the control group,the 8th weekend model group and the 12th weekend model group were 0.169 ± 0.010,0.649 ± 0.071,0.781 ±0.077.Comparing the differences among the 3 groups were statistically significant (F =27.72,P ＜ 0.01).The LVEF (％) results of the control group,the 8th weekend model group and the 12th weekend model group were 75.41 ± 2.02,53.25 ±3.74,39.21 ±6.13.Comparing the differences among the 3 groups were statistically significant(F =154.87,P ＜0.01).There was a negative correlation between the ASK1 expression and LVFE in model group at the end of 12weeks(r =-0.86,P ＜ 0.01).Conclusions The ASK1 expression in myocardium of the DCM group increases obviously,thus apoptosis signal-regulating probably participates in the pathological process of DCM induced by ASK1.