亚硝酰氢对心力衰竭大鼠心脏保护作用的研究

The protective effect of Nitroxylon the heart of rats with heart failure

目的 探讨亚硝酰氢对心力衰竭大鼠心脏是否有保护作用.方法 选取50只雄性Wistar大鼠,从中随机抽取42只采用结扎左冠状动脉前降支方法制作心肌梗死后心力衰竭模型,剩余8只作为假手术组（Sham组,n=8）.术后3d手术组大鼠存活17只,随机分为心力衰竭对照组（HF组,n=8）和亚硝酰氢治疗组（HNO组,n=9）.术后第3天开始给予HNO组大鼠腹腔注射亚硝酰氢供体Angeli＇s salt,HF组及Sham组均给予等量生理盐水;4周后用ELISA法检测大鼠外周血N末端B型利钠肽（NT-proBNP）水平,超声心动图检测大鼠心功能,左心压力导管检测大鼠血流动力学改变,最后处死大鼠,计算心体指数.结果 术后4周HNO治疗组大鼠与HF组相比,NT-ProBNP、左心室舒张末压（LVEDP）明显降低[（385.65±43.50）pg/ml比（496.13±52.80）pg/ml,P＜0.01;（17.49±2.04）mm Hg比（21.19±1.91）mm Hg,P＜0.05],左心室射血分数（LVEF）[（52.88±5.46）％比（39.71±3.64）％,P＜0.01]、左心室短轴收缩率（LVFS）[（23.75±3.11）％比（16.57±1.72）％,P＜0.01]、左心室内压力最大上升速率（＋dp/dt）[（3029.13±634.12）mm Hg/s比（2347.43±451.38）mm Hg/s,P＜0.05]、左心室内压力最大下降速率（-dp/dt）[（2896.50±642.66）mm Hg/s比（2169.29±433.17）mm Hg/s,P＜0.05]明显增加,心体指数（HW/BW）、左心室舒张末内径（LVEDd）、左心室收缩压（LVSP）无明显差异[（2.97±0.17）g/kg比（2.98±0.16）g/kg,（7.19±0.87）mm比（7.66±0.84）mm,（131.38±9.47）mm Hg比（130.57±11.46）mm Hg,P均＞0.05].结论 亚硝酰氢可以增强心力衰竭大鼠心脏功能,改善血流动力学,降低外周血NT-ProBNP水平,对心力衰竭大鼠心脏起保护作用.

Objective To explore whether nitroxyl has a protective effect on the heart of rats with heart failure. Methods 50 male Wistar rats were selected and 42 rats out of them were selected to build heart failure model after acute myocardial infarction by a ligation of anterior descending branch, 17 rats survived, which were randomly divided into heart failure group（HF group, n=8） and nitroxyl-treated group（HNO group, n=9）, the re- maining 8 rats were taken as a sham operation group（n=8 ）, Nitroxyl donor Angeli＇s salt were intraperitoneal injec- tion to HNO group from the day 3 after operation, the HF group and the sham group were given the same dose normal saline, 4 weeks later, the level of NT-ProBNP in rats＇ peripheral blood had been tested by ELISA method, the ultrasonic cardiogram and the left-heart pressure transducer were used to test the rats＇ cardiac func- tion, the rats were eventually killed to calculate the heart-body index. Results At week 4 after operation, com- pared with heart failure group, the nitroxyl-treated group had a significant decline in NT-proBNP,LVEDP [（385.65±43.50）pg/ml vs （496.13±52.80）pg/ml, P〈0.01, （17.49±2.04）mm Hg vs （21.19±1.91）mm Hg, P〈 0.05 ], and a significant increase in LVEF,LVFS＋dp/dt,-dp/dt [ （52.88±5.46）% vs （39.71±3.64）%, P〈0.01, （23.75±3.11）% vs （16.57±1.72）%, P〈0.01, （3029.13±634.12）mm Hg/s vs （2347.43±451.38）mm Hg/s, P〈0.05, （2896.50±642.66）mm Hg/s vs（2169.29±433.17）mm Hg/s, P〈0.05], the difference in HW/BW,LVEDd, LVSP between the two groups were not significant [（2.97±0.17）g/kg vs （2.98±0.16）g/kg, （7.19±0.87）mm vs （7.66±0.84）mm,（131.38±9.47）mm Hg vs（130.57±11.46）mm Hg, P〉0.05]. Conclusion Nitroxyl is able to en- hance the cardiac function of the rats having heart failure, improve the hemodynamies, reduce the level of NT- ProBNP in peripheral blood, exert a protective effect on the heart of rats having heart failure.