Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK.
Pharmacol Res. 2010 Jun;61(6):564-70. doi: 10.1016/j.phrs.2010.01.008. Epub 2010 Jan 18.
It is a consensus view that a strategy to increase heart resistance to ischaemia-reperfusion is a warranted. Here, based on our previous study, we have hypothesized that a nicotinamide-rich diet could increase myocardial resistance to ischaemia-reperfusion. Therefore, the purpose of this study was to determine whether nicotinamide-rich diet would increase heart resistance to ischaemia-reperfusion and what is the underlying mechanism. Experiments have been done on mice on control and nicotinamide-rich diet (mice were a week on nicotinamide-rich diet) as well as on transgenic mice overexpressing SUR2A (SUR2A mice), a regulatory subunit of cardioprotective ATP-sensitive K(+) (K(ATP)) channels and their littermate controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR, whole heart and single cell resistance to ischaemia-reperfusion and severe hypoxia was measured by TTC staining and laser confocal microscopy, respectively. Nicotinamide-rich diet significantly decreased the size of myocardial infarction induced by ischaemia-reperfusion (from 42.5+/-4.6% of the area at risk zone in mice on control diet to 26.8+/-1.8% in mice on nicotinamide-rich diet, n=6-12, P=0.031). The cardioprotective effect of nicotinamide-rich diet was associated with 11.46+/-1.22 times (n=6) increased mRNA levels of SUR2A in the heart. HMR1098, a selective inhibitor of the sarcolemmal K(ATP) channels opening, abolished cardioprotection afforded by nicotinamide-rich diet. Transgenic mice with a sole increase in SUR2A expression had also increased cardiac resistance to ischaemia-reperfusion. We conclude that nicotinamide-rich diet up-regulate SUR2A and increases heart resistance to ischaemia-reperfusion.
人们普遍认为，增加心脏对缺血再灌注的抵抗力是有必要的。在这里，基于我们之前的研究，我们假设富含烟酰胺的饮食可以增加心肌对缺血再灌注的抵抗力。因此，本研究的目的是确定富含烟酰胺的饮食是否会增加心脏对缺血再灌注的抵抗力，以及其潜在的机制。我们在对照组和富含烟酰胺的饮食组（小鼠接受富含烟酰胺的饮食一周）以及过表达 SUR2A（调节型 ATP 敏感性 K+（KATP）通道的亚基）的转基因小鼠及其同窝对照（WT）小鼠上进行了实验。通过实时 RT-PCR 测量心脏组织中的 mRNA 水平，通过 TTC 染色和激光共聚焦显微镜分别测量全心脏和单个细胞对缺血再灌注和严重缺氧的抵抗力。富含烟酰胺的饮食显著减少了缺血再灌注引起的心肌梗死面积（从对照组饮食小鼠的危险区面积的 42.5+/-4.6%减少到富含烟酰胺饮食组的 26.8+/-1.8%，n=6-12，P=0.031）。富含烟酰胺的饮食的心脏保护作用与心脏中 SUR2A 的 mRNA 水平增加 11.46+/-1.22 倍（n=6）有关。HMR1098，一种肌浆网 KATP 通道开放的选择性抑制剂，消除了富含烟酰胺的饮食所提供的心脏保护作用。SUR2A 表达仅增加的转基因小鼠也增加了心脏对缺血再灌注的抵抗力。我们得出结论，富含烟酰胺的饮食上调 SUR2A 并增加心脏对缺血再灌注的抵抗力。
