P物质对急性心肌缺血大鼠心功能的影响

Effects of substance P on left ventricular functions in rats with acute myocardial infarction

目的观察P物质对急性心肌缺血后大鼠心功能的影响。方法健康成年雄性SD大鼠48只,体重250-300 g,分在体实验和离体实验两部分,每部分随机分为3组(n=8):手术对照组(sham组)、急性结扎冠脉(coronary artery occlusion,CAO)组和药物干预组。药物干预在体实验干预组(D-SP组)使用神经激肽-1(NK-1)受体拮抗剂(D-SP),离体实验干预组(SP组)使用P物质(substance P,SP)。CAO组和药物干预组在体和离体模型均采用结扎冠状动脉左前降支,手术对照组除不结扎冠状动脉外,其余操作同CAO组。CAO前按照不同分组分别给予生理盐水、SP(离体,10-6mol/L)或D-SP(在体,10-7mol/L)。观察记录药物干预前5 min到CAO后60 min内的左心室心功能参数,包括:左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室最大收缩速率(LV+dP/dtmax)、左心室最大舒张速率(LV-dP/dtmax)和HR。计算左心室发展压(LVDP=LVSP-LVEDP),同时记录心电图。结果与sham组及CAO组相比,CAO前SP和D-SP干预对左室心功能各项参数的影响无统计学意义(P>0.05)。在体实验中,与CAO组相比,NK-1受体拮抗剂(D-SP)组CAO后LV+dP/dtmax显著升高(P<0.05),降低LV-dP/dtmax(P<0.05)。离体研究中,与CAO组相比,SP组CAO后LVEDP明显升高(P<0.05)。SP和D-SP对CAO后心率变化无显著影响(P>0.05)。结论 P物质通过激活NK-1受体减弱急性心肌缺血后大鼠左心室收缩和舒张功能。

Abstract： Objective To investigate the role of substance P （SP） in the regulation of left ventricular functions in acute myocardial infarction rats.Methods Forty-eight Sprague-Dawley male rats weighing 250-300 g,were assigned into in vivo and in vitro experiments.The models of acute myocardial infarction in vivo and in vitro were carried out by ligating the left anterior descending coronary artery.Sham-operated rats underwent the identical surgical procedure except that the suture was not tightened around the coronary artery.The rats were divided into three groups in two experiments respectively：sham group,coronary artery occlusion （CAO） group and D-SP group or SP group.The rats in D-SP group and SP-CAO group were pretreated with a specific antagonist of NK-1 receptor （D-SP,10-7 mol/L,1 ml/kg,intravenous injection,at 15 min before CAO,in vivo） and SP （10-6 mol/L,administrated continuously for 15 min before CAO,in vitro）,respectively,while the rats in sham group and CAO group were given the same volume of physiological saline as scheduled.Electrocardiograms and intra-ventricular pressures were monitored during the study.Left ventricular systolic pressure （LVSP）,left ventricular end-diastolic pressure （LVEDP）,the maximum rise rate of left ventricular pressure （LV ＋ dP/dtmax）,the maximum descending rate of left ventricular pressure （LV-dP/dtmax） and heart rate（HR） were continuously recorded.Left ventricular development pressure（LVDP） was calculated （=LVSP-LVEDP）.Results Pretreatment with D-SP in in vivo rats significantly increased LV ＋ dP/dtmax and decreased LV-dP/dtmax after CAO （P 〈 0.05）.Pretreatment of the isolated CAO hearts with SP significantly increased LVEDP （P 〈 0.05）.SP or D-SP produced no effects on HR after CAO（P 〉 0.05）.Conclusion SP could attenuate left ventricular systolic and diastolic functions after acute myocardial infarction in rat heart by activating NK-1 receptor.