缬沙坦对心力衰竭幼鼠心功能及肌浆网Ca^(2+)-ATP酶活性的影响

Effect of valsartan on heart function and activity of myocardial sarc-oplasmic reticulum Ca^(2+)-ATPase in junior rat with heart failure

目的:研究缬沙坦对心力衰竭(Heart failure,HF)(简称心衰)幼鼠心功能及肌浆网(Sarcoplasmic reticulum,SR)Ca2+-ATP酶(Ca2+-ATPase,SERCA2a)活性和Ca2+重吸收量的影响。方法:采用腹主动脉-下腔静脉造瘘术建立幼鼠心衰模型,术后8周随机分为2组:心衰组和缬沙坦治疗组,另设假手术组;缬沙坦灌胃给药,每日观察幼鼠的呼吸、皮毛颜色、活动量等发育情况;术后12周高频超声检测心功能;定磷法测定SR膜SERCA2a酶活性;荧光分光光度仪检测钙离子(Ca2+)的重吸收量。结果:与假手术组(n=15)比较,对照组(n=20)幼鼠左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)均明显升高(P<0.01),左室射血分数(EF)、左室短轴缩短率(FS)均明显降低(P<0.01);与对照组比较,缬沙坦治疗组(n=15),LVIDd、LVIDs、LVEDV、LVESV均明显降低(P<0.01),FS、EF升高(P<0.01);对照组的SERCA2a活性较假手术组明显降低(P<0.01),而经缬沙坦治疗后,酶活性接近假手术组(P>0.05);若分别向含有3组SR的缓冲液加入0.5mmol/L ATP后,对照组的Ca2+的重吸收量同假手术组比较,明显降低(P<0.01),与对照组比较,缬沙坦组Ca2+的重吸收量显著提高(P<0.01)。结论:对照组幼鼠心功能显著降低,心肌细胞SERCA2a活性降低,Ca2+重拾量减少,缬沙坦可提高SERCA2a的Ca2+重拾能力,改善细胞收缩、舒张功能,进一步提高心脏功能并有效抑制心室重塑。

Objective： To explore the effect of Valsartan on heart function and a-ctivity of myocardial sarcoplasmic reticulum Ca^2＋ ATPase in junior rat with heart failure（HF）. Methods： The animal model of congestive heart failure was established byiistulation of abdominal aorta and inferior vena cava.Rats were randomly divided into 2 groups after 8 weeks of operation：rats without treatment as control group（n=20）,rats treated with Yalsartan as valsartan group（n=15）.Sham-operated was taken as normal control group（n=15）.Valsartan was adminis-tered through direct gastric gavage. The high frequency ultrasound was performed 4 weeks after treatment.Myocardial SR was fractionated with velocity centrifugation. Enzyme activity of SERCA2a in SR was detected with ultraviolet spectrophotometre（U V）.The time course of Ca^2＋ uptake was determined by fluorescent spectrophotometry. Results： Compared with the sham-operated group,left ventricular internal dimension diastole（LVIDd）,left ventricularinternal dimension systole （LVIDs）,left ventricular end-diastolic volume（LVEDV ）, and left ventricular end-systolic volume （LVESV） were all significantly increased（P〈0.01 ）,while left ventricular ejection fraction（LVEF）,and left ventricular fractional shortening（LVFS）were decreased（P〈0.01 ） in control group.LVIDd,LVIDs,LVEDV,LVESV were all prominently decresed（P〈0.01 ）, while LVEF,and LVFS were inreased（P〈0.01 ） in Valsartan group when compared with control group. Enzyme activity of SERCA2a decreased in control group as compared with other two groups. After adding ATP to the buffer including SR of three groups,Ca^2＋ uptake was significantly decreased（P〈0.01 ） in control group,and it increased almost to normal level in Valsartan group. Conclusion： Heart function and the enzyme activity of SERCA2a decreased in junior rat with heart failure,Valsartan can anastate the uptake of Ca^2＋ by increasing enzyme activity of SERCA2a,and improve cardiac contractility and finally heart function in junior rat with heart failure.