心力衰竭幼鼠心肌CaMKII表达及药物干预研究

Effect of Valsartan on the Expression of CaMKII in Juvenile Rat with Heart Failure

摘要:

【摘 要】目的：研究缬沙坦（Valsartan）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 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幼鼠的心力衰竭模型，同时设假手术组；术后4周将心衰鼠随机分为心衰组和缬沙坦治疗组，缬沙坦组每日灌胃给药，心衰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室收缩和舒张末期内径（LVIDs、LVIDd）、左室收缩和舒张末期容积（LVESV、LVEDV）、左室射血分数（LVEF）、左室短轴收缩率（LVFS）；左、右心室重量指数（LVMI、RVMI）；Western blot检测CaMKII及其亚型表达情况。结果：与假手术组（n=8）比较，心衰组（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表达没有显著差异（P >0.05）。结论：心力衰竭幼鼠心室肌上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:

[Abstract] Objective：To explorer the effect of valsartan on the expression of CaMKII in Juvenile rat with Heart Failure(HF). Methods: The animal model of heart failure was established by abdominal aortic constriction （AAC）in 3 weeks old SD rats ，while the establishment of the sham operation group. 4 weeks later, the rats with heart failure were randomly divided into 2 group：HF group，valsartan treatment group. Valsartan were taken through direct gastric gavage everyday. HF group and sham operation group were given placebos.8 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 the sham operation group (n=8)， 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)，the expression of CaMKII was increased by 1.95 fold (F =7.541，P =0.026), the expression of CaMKII subunits (δB δ9) was increased to 1.93 fold (F =7.042，P =0.029)，and the expression of CaMKIIδC was increased to 1.93 fold (F =6.714，P =0.045) in HF group(n=10). After the treatment，no significant difference of LVIDs、LVIDd 、LVESV、LVEDV 、LVEF 、LVFS 、LVMI and the expression of CaMKII was found between valsartan treatment group and sham operation group（P >0.05）. Conclusion: The expression of CaMKII in juvenile rats with HF was increased. Valsartan can improve cardiac contractile function with heart failure, which may be associated with reduced expression of CaMKII in ventricular myocytes .