心力衰竭幼鼠心肌钙调素依赖性蛋白激酶Ⅱ表达及药物干预研究

Expressions of calmodulin-dependent protein kinaseⅡ in juvenile rats with heart failure and the valsartan intervention

摘要:

目的：研究缬沙坦对心力衰竭（heart failure，HF）幼鼠心室肌内钙调素依赖性蛋白激酶Ⅱ（calmodulin-dependent protein kinaseⅡ，CaMKⅡ）表达的影响。方法：采用腹主动脉部分缩窄（abdominal aortic constriction，AAC）的方法建立3周龄SD幼鼠的HF模型，同时设假手术组；术后4周将HF鼠随机分为HF组和缬沙坦治疗组，缬沙坦组每日灌胃给药，HF组和假手术组给予安慰剂；术后8周使用高频超声检测大鼠左心室收缩和舒张末期内径（left ventricular-internal dimension systole，LVIDs；left ven－tricular-internal diastolic diameter，LVIDd）、左心室收缩和舒张末期容积（left ventricular end-systolic volume，LVESV；left ven－tricular end diastolic volume，LVEDV）、左心室射血分数（left ventricular ejection fraction，LVEF）、左心室短轴收缩率（left ventricu－lar fractional shortening，LVFS）；左、右心室重量指数（left ventricular mass index，LVMI；right ventricular mass index，RVMI）；West－ern blot检测CaMKⅡ及其亚型表达情况。结果：与假手术组（n=8）比较，HF组（n=10）LVIDs、LVESV均明显升高（F=21.082，P<0.001；F=14.178，P=0.001），LVEF、LVFS均明显降低（F=103.766，P<0.001；F=62.953，P<0.001），LVIDd、LVEDV无明显差异；LVMI明显增加（F=13.272，P =0.01）；心室肌细胞内CaMKⅡ表达升高1.95倍（F=7.541，P=0.026），CaMKⅡ亚型（δB+δ9）表达升高1.93倍（F=7.042，P=0.029），CaMKⅡδC表达升高1.93倍（F=6.714，P=0.045）；经缬沙坦治疗后，缬沙坦组（n=8）与假手术组比较，超声结果（LVIDs、LVIDd、LVESV、LVEDV、LVEF、LVFS）、LVMI和CaMKⅡ表达差异无统计学意义（P >0.05）。结论：HF幼鼠心室肌上CaMKⅡ表达增高；缬沙坦改善HF心脏收缩功能，可能与其部分下调心室肌细胞内CaMKⅡ的表达有关。

Abstract:

Objective：To explore the effects of valsartan on expressions of calmodulin-dependent protein kinaseⅡ（CaMKⅡ） in juve－nile rats with heart failure（HF）. Methods：HF animal model was established by abdominal aortic constriction（AAC） in 3 week-old SD rats while sham operation group was established. Four weeks later，rats with HF were randomly divided into 2 groups：HF group and valsartan treatment group. Rats in valsartan treatment group were given valsartan through direct gastric gavage everyday while those in HF group and sham operation group were given placebos. Eight weeks later，high frequency ultrasound was employed to measure left ventricular-internal dimension systole（LVIDs），left ventricular-internal diastolic diameter（LVIDd），left ventricular end-systolic volume（LVESV），left ventricular end diastolic volume（LVEDV），left ventricular ejection fraction（LVEF），left ventricular fractional shortening（LVFS） of rats. Left and right ventricular mass index（LVMI，RVMI） were calculated. Western blot was applied to detect the expression of CaMKⅡ and subunits. Results：Compared with those in sham operation group，LVIDs and LVESV were increased（F=21.082，P<0.001；F=14.178，P=0.001），LVEF and LVFS were all significantly decreased（F=103.766，P<0.001；F=62.953，P<0.001），LVMI was increased（F=13.272，P=0.01），expressions of CaMKⅡ were increased by 1.95 folds（F=7.541，P=0.026），expressions of CaMKⅡ subunits（δB+δ9） were increased by 1.93 folds（F=7.042，P=0.029） and expressions of CaMKⅡδC was increased by 1.93 folds（F=6.714，P=0.045） in HF group. After the treatment，no significant difference in LVIDs，LVIDd，LVESV，LVEDV，LVEF，LVFS，LVMI and expressions of CaMKⅡ was found between valsartan treatment group and sham operation group（P >0.05）. Conclusions：Expressions of CaMKⅡ in juvenile rats with HF are increased. Valsartan can improve cardiac contractile function of rats with HF，which may be associated with reduced expressions of CaMKⅡ in ventricular myocytes.