烟酰胺腺嘌呤二核苷酸通过改善心肌微循环减少心肌缺血/再灌注损伤的研究

Role of Nicotinamide Adenine Dinucleotide in Reducing Myocardial Ischemia/reperfusion Injury by Improving Myocardial Microcirculation

目的探讨烟酰胺腺嘌呤二核苷酸(NAD+)在心肌缺血/再灌注中的作用及机制。方法 14只巴马小型猪随机分为2组(实验组,n=7,对照组,n=7),采用经皮球囊封堵冠状动脉建立心肌缺血/再灌注模型,再灌注前实验组给予20 mg/kg NAD(+)。再灌注后2 h及4周后分别行心肌核素显像记录心肌灌注总静息评分(summed rest score,SRS)及节段室壁运动距离。4周后行病理分析评估毛细血管密度。结果实验组心肌缺血程度较对照组轻(P=0.017),具有更低的SRS(P=0.036)。术后4周随访心功能,实验组心尖部缺血心肌,包括节段17(5.95±2.18)mm vs(1.66±1.90)mm,P=0.016,节段15(8.88±3.57)mm vs (3.68±2.97)mm,P=0.048),节段14(9.43±3.67)mm vs (1.90±1.73)mm,P=0.004)及节段13(5.28±2.72)mm vs (1.24±0.60)mm,P=0.014),较对照组运动能力更佳。此外,病理检测提示实验组较对照组微循环密度更高(1.16±0.38)%vs(0.83±0.54)%,P=0.019)。结论外源性补充NAD(+)通过促进血管生成,改善冠脉微循环,减少心肌缺血/再灌注损伤,改善心肌灌注及心功能。

Objective To discuss the role and mechanism of nicotinamide adenine dinucleotide[NAD(+)]in ischemia/reperfusion.Methods 14 Bama miniature pigs were treated by coronary balloon occlusion to set up the myocardial ischemia/reperfusion models and then were randomly divided into 2 groups:experiment group and control group,7 in each;before reperfusion 20 mg/kg NAD(+)was given to the pigs in experiment group;at the time point of 2 hours and 4 weeks after reperfusion,myocardial perfusion tomographic imaging was performed and the summed rest scores(SRS)and regional left ventricular wall motion were recorded;4 weeks after reperfusion,pathological study was made to assess the capillary density.Results Myocardial ischemia in experiment group was less severe than that in control group(P=0.017)and the SRS were much lower than those in control group(P=0.036);the follow-up 4 weeks after surgery indicated that the motion of apical ischemic myocardium in experiment group was much better than that in control group,including the segment-17[(5.95±2.18)mm vs(1.66±1.90)mm,P=0.016],the segment-15[(8.88±3.57)mm vs(3.68±2.97)mm,P=0.048],the segment-14[(9.43±3.67)mm vs(1.90±1.73)mm,P=0.004]and the segment-13[(5.28±2.72)mm vs(1.24±0.60)mm,P=0.014];pathological study indicated that microcirculation density in experiment group was higher than that in control group[(1.16±0.38)%vs(0.83±0.54)%,P=0.019].Conclusions Supplementation of NAD(+)can improve coronary microcirculation,myocardial perfusion and heart function,and can reduce myocardial ischemia/reperfusion injury by promoting angiogenesis.