【摘要】：目的使用亞硝酰氫干預心力衰竭大鼠,觀察其對心力衰竭大鼠心臟功能是否有保護作用,并探討其可能作用機制。方法選取50只大鼠,其中42只通過結扎左冠狀動脈前降支方法制備心肌梗死后心力衰竭模型,術后4周存活18只,將其隨機分為心力衰竭組(HF組,n=9)、Angeli’s salt治療組(AS組,n=9);其余8只作為假手術組(Sham組,n=8);給予AS組大鼠HNO供體Angeli’s salt 1mg/kg/d腹腔注射;HF組和Sham組均給予等量生理鹽水;施加干預措施2周時,HF組大鼠死亡2只,AS組死亡1只,其余大鼠生存狀態(tài)差,遂結束實驗。檢測大鼠外周血NT-ProBNP水平及心臟超聲,測量參數(shù)包括左心室舒張末期內徑(LVEDd)、左心室收縮末期內徑(LVEDs)、左心室射血分數(shù)(LVEF)、左心室短軸收縮率(LVFS)。用動脈導管檢測大鼠左心室收縮壓(LVSP)、左心室舒張末壓(LVEDP)、左心室內壓力最大上升速率(+dp/dt)、左心室內壓力最大下降速率(-dp/dt);最后用Western blot檢測心臟左心室非梗死區(qū)組織肌漿網鈣泵(SERCA2a)蛋白的表達,生化試劑盒檢測SERCA2a蛋白活性。結果藥物干預前,與Sham組相比,HF組大鼠LVEDd、LVEDs、NT-ProBNP均明顯增加(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均明顯減低(49.89±2.85vs81.25±2.19、20.67±1.50vs42.88±2.42,p0.01);與HF組相比,AS組大鼠LVEDd、LVEDs、LVEF、LVFS、NT-ProBNP均無明顯差異(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)。藥物干預后,與Sham組相比,HF組大鼠LVEDP明顯增加(18.39±1.43vs7.18±0.91,p0.01),+dp/dt、-dp/dt明顯減低(2044.14±236.82vs3950.13±264.29、1966.43±225.43vs3842.25±241.07,p0.01);心臟組織SERCA2a蛋白表達量明顯減少(0.28±0.031vs0.49±0.039,p0.01),活性明顯減低(7.47±1.32vs14.34±1.35,p0.01);LVSP無明顯差異(132.86±8.93vs138.75±9.77,p0.05)。與HF組相比,AS組大鼠LVEF、LVFS、+dp/dt、-dp/dt明顯增加(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明顯減低(393.88±23.37vs437.53±24.12、15.48±1.23vs18.39±1.43,p0.05),SERCA2a蛋白活性明顯增強(9.23±1.44vs7.47±1.32,p0.05),而LVEDd、LVEDs、LVSP、SERCA2a蛋白表達量均無明顯差異(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)。結論1.HNO可以增加心力衰竭大鼠心臟射血分數(shù),降低外周血NT-ProBNP濃度,改善血流動力學,對心力衰竭大鼠心臟有保護作用。2.心力衰竭大鼠心臟組織SERCA2a蛋白表達量減少,活性減低。3.HNO可增加心力衰竭大鼠SERCA2a蛋白活性,但對SERCA2a蛋白的表達無明顯影響。
[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. 緇撴灉鑽墿騫查鍓，

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