亚硝酰氢对心力衰竭大鼠心脏功能及肌浆网钙泵的影响

发布时间：2018-08-15 13:16

【摘要】：目的使用亚硝酰氢干预心力衰竭大鼠,观察其对心力衰竭大鼠心脏功能是否有保护作用,并探讨其可能作用机制。方法选取50只大鼠,其中42只通过结扎左冠状动脉前降支方法制备心肌梗死后心力衰竭模型,术后4周存活18只,将其随机分为心力衰竭组(HF组,n=9)、Angeli’s salt治疗组(AS组,n=9);其余8只作为假手术组(Sham组,n=8);给予AS组大鼠HNO供体Angeli’s salt 1mg/kg/d腹腔注射;HF组和Sham组均给予等量生理盐水;施加干预措施2周时,HF组大鼠死亡2只,AS组死亡1只,其余大鼠生存状态差,遂结束实验。检测大鼠外周血NT-ProBNP水平及心脏超声,测量参数包括左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVEDs)、左心室射血分数(LVEF)、左心室短轴收缩率(LVFS)。用动脉导管检测大鼠左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左心室内压力最大上升速率(+dp/dt)、左心室内压力最大下降速率(-dp/dt);最后用Western blot检测心脏左心室非梗死区组织肌浆网钙泵(SERCA2a)蛋白的表达,生化试剂盒检测SERCA2a蛋白活性。结果药物干预前,与Sham组相比,HF组大鼠LVEDd、LVEDs、NT-ProBNP均明显增加(7.04±0.42vs5.10±0.32、5.59±0.42vs2.92±0.30、377.97±20.47vs83.48±4.69,p0.01),LVEF、LVFS均明显减低(49.89±2.85vs81.25±2.19、20.67±1.50vs42.88±2.42,p0.01);与HF组相比,AS组大鼠LVEDd、LVEDs、LVEF、LVFS、NT-ProBNP均无明显差异(7.09±0.42vs7.04±0.42、5.62±0.43vs5.59±0.42、50.22±2.64vs49.89±2.85、20.89±1.17vs20.67±1.50、381.20±20.81vs377.97±20.47,p0.05)。药物干预后,与Sham组相比,HF组大鼠LVEDP明显增加(18.39±1.43vs7.18±0.91,p0.01),+dp/dt、-dp/dt明显减低(2044.14±236.82vs3950.13±264.29、1966.43±225.43vs3842.25±241.07,p0.01);心脏组织SERCA2a蛋白表达量明显减少(0.28±0.031vs0.49±0.039,p0.01),活性明显减低(7.47±1.32vs14.34±1.35,p0.01);LVSP无明显差异(132.86±8.93vs138.75±9.77,p0.05)。与HF组相比,AS组大鼠LVEF、LVFS、+dp/dt、-dp/dt明显增加(53.25±2.43vs48.43±3.51、22.38±1.51vs20.00±1.63、2412.00±357.35vs2044.14±236.82、2302.25±335.54vs1966.43±225.43,p0.05),NT-ProBNP、LVEDP明显减低(393.88±23.37vs437.53±24.12、15.48±1.23vs18.39±1.43,p0.05),SERCA2a蛋白活性明显增强(9.23±1.44vs7.47±1.32,p0.05),而LVEDd、LVEDs、LVSP、SERCA2a蛋白表达量均无明显差异(7.28±0.48vs7.46±0.55、5.65±0.47vs5.98±0.57、136.38±9.52vs132.86±8.93、0.29±0.036vs0.28±0.031,p0.05)。结论1.HNO可以增加心力衰竭大鼠心脏射血分数,降低外周血NT-ProBNP浓度,改善血流动力学,对心力衰竭大鼠心脏有保护作用。2.心力衰竭大鼠心脏组织SERCA2a蛋白表达量减少,活性减低。3.HNO可增加心力衰竭大鼠SERCA2a蛋白活性,但对SERCA2a蛋白的表达无明显影响。
[Abstract]:Objective to investigate the protective effect of nitrite hydrogen on heart function in rats with heart failure and to explore its possible mechanism. Methods A total of 50 rats were selected. Among them, 42 rats were induced to have heart failure after myocardial infarction by ligation of left anterior descending coronary artery. 18 rats survived 4 weeks after operation. They were randomly divided into two groups: heart failure group (HF group) and Angelius salt treatment group (as group), the other 8 rats were used as sham-operation group (Sham group), the rats in as group were given HNO donor Angeli's salt 1mg/kg/d intraperitoneal injection of HF group and Sham group, and the other 8 rats were given the same amount of normal saline. Two weeks after intervention, 2 rats in HF group died and 1 rat died in as group, and the other rats were in poor living condition, so the experiment was completed. NT-ProBNP level in peripheral blood and echocardiography were measured in rats. Parameters included left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular ejection fraction (LVEF), left ventricular short-axis contraction rate (LVFS). The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular maximum pressure rise rate (dp/dt), left ventricular maximum pressure decrease rate (-dp / DT) were measured by arterial catheter in rats. Finally, the left ventricular non-infarct tissue muscle was detected by Western blot. Expression of calcium pump (SERCA2a) protein, The activity of SERCA2a protein was detected by biochemical kit. 缁撴灉鑽�鐗╁共棰勫墸�

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