Hjortbak Marie Vognstoft, Hjort Johanne, Povlsen Jonas Agerlund, Jensen Rebekka Vibjerg, Støttrup Nicolaj Brejnholdt, Laursen Mia R, Jespersen Nichlas Riise, Løfgren Bo, Bøtker Hans Erik
Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Blvd. Aarhus N, Denmark.
Department of Forensic Medicine, Aarhus University Hospital, Skejby, Palle Juul-Jensens Blvd. Aarhus N, Denmark.
PLoS One. 2018 Feb 23;13(2):e0192981. doi: 10.1371/journal.pone.0192981. eCollection 2018.
Augmented mortality and morbidity following an acute myocardial infarction in patients with diabetes mellitus Type 2 (T2DM) may be caused by increased sensitivity to ischemia reperfusion (IR) injury or altered activation of endogenous cardioprotective pathways modified by T2DM per se or ischemic preconditioning (IPC). We aimed to investigate, whether the duration of T2DM influences sensitivity against IR injury and the efficacy of IPC, and how myocardial glucose oxidation rate was involved. Male Zucker diabetic fatty rats (homozygote (fa/fa)) at ages 6-(prediabetic), 12- (onset diabetes) and 24-weeks of age (late diabetes) and their age-matched non-diabetic controls (heterozygote (fa/+) were subjected to IR injury in the Langendorff model and randomised to IPC stimulus or control. T2DM rats were endogenously protected at onset of diabetes, as infarct size was lower in 12-weeks T2DM animals than in 6- (35±2% vs 53±4%; P = 0.006) and 24-weeks animals (35±2% vs 72±4%; P<0.0001). IPC reduced infarct size in all groups irrespective of the presence of T2DM and its duration (32±3%; 20±2%; 36±4% respectively; (ANOVA P<0.0001). Compared to prediabetic rats, myocardial glucose oxidation rates were reduced during stabilisation and early reperfusion at onset of T2DM, but these animals retained the ability to increase oxidation rate in late reperfusion. Late diabetic rats had low glucose oxidation rates throughout stabilisation and reperfusion. Despite inherent differences in sensitivity to IR injury, the cardioprotective effect of IPC was preserved in our animal model of pre-, early and late stage T2DM and associated with adaptations to myocardial glucose oxidation capacity.
2型糖尿病（T2DM）患者急性心肌梗死后死亡率和发病率增加，可能是由于对缺血再灌注（IR）损伤的敏感性增加，或由T2DM本身或缺血预处理（IPC）改变的内源性心脏保护途径的激活改变所致。我们旨在研究T2DM的病程是否会影响对IR损伤的敏感性和IPC的疗效，以及心肌葡萄糖氧化率是如何参与其中的。将6周龄（糖尿病前期）、12周龄（糖尿病发病期）和24周龄（糖尿病晚期）的雄性Zucker糖尿病脂肪大鼠（纯合子（fa/fa））及其年龄匹配的非糖尿病对照（杂合子（fa/+））在Langendorff模型中进行IR损伤，并随机分为IPC刺激组或对照组。T2DM大鼠在糖尿病发病时具有内源性保护作用，因为12周龄的T2DM动物梗死面积低于6周龄（35±2%对53±4%；P = 0.006）和24周龄动物（35±2%对72±4%；P<0.0001）。无论是否存在T2DM及其病程如何，IPC均能降低所有组的梗死面积（分别为32±3%；20±2%；36±4%；（方差分析P<0.0001）。与糖尿病前期大鼠相比，T2DM发病时稳定期和早期再灌注期间心肌葡萄糖氧化率降低，但这些动物在晚期再灌注时仍保留增加氧化率的能力。糖尿病晚期大鼠在整个稳定期和再灌注期葡萄糖氧化率均较低。尽管对IR损伤的敏感性存在固有差异，但IPC的心脏保护作用在我们的T2DM前期、早期和晚期动物模型中得以保留，并与心肌葡萄糖氧化能力的适应性变化有关。
