急性心肌梗死(AMI)导致心脏功能障碍,也引起脑功能障碍和病理。促红细胞生成素(EPO)的神经保护作用,控制红细胞产生的激素,已在脑缺血/再灌注(I/R)损伤的情况下显示。然而,EPO对心脏I/R损伤引起的脑病变的影响尚未研究。我们假设EPO的给药通过减少外周和脑氧化应激减轻由心脏I/R损伤引起的脑损伤,保留小胶质细胞形态,减轻海马坏死,减少海马细胞凋亡,和海马发育不良。雄性Wistar大鼠(n=38)分为两组,假手术(n=6)和心脏I/R(n=32)。所有接受心脏I/R手术的大鼠随机分为4个亚组(n=8/组):载体,EPO预处理,在缺血期间给予EPO,在再灌注开始时给予EPO。通过静脉注射以5000单位/kg的剂量给予EPO。左心室功能,氧化应激,脑线粒体功能,小胶质细胞形态学,海马坏死,海马细胞凋亡,测量海马可塑性。EPO给药发挥了有益的抗氧化作用,抗炎,和抗心脏I/R对大脑的抗凋亡作用。在心脏缺血前给予EPO可通过减弱LV功能障碍对心脏I/R损伤产生最大的神经保护作用。减少外周和脑氧化应激,以及小胶质细胞活化的减弱,脑线粒体功能障碍,凋亡,和坏死,导致改善心脏I/R条件下的海马发育不良。EPO预处理对心脏I/R引起的脑部病理具有最大的益处。
Acute myocardial infarction (AMI) leads to cardiac dysfunction and also causes brain dysfunction and pathology. The neuroprotective effects of erythropoietin (EPO), the hormone controlling the production of red blood cells, have been shown in case of cerebral ischemic/reperfusion (I/R) injury. However, the effects of EPO on the brain pathologies induced by cardiac I/R injury have not been investigated. We hypothesized that the administration of EPO attenuates brain damage caused by cardiac I/R injury through decreasing peripheral and brain oxidative stress, preserving microglial morphology, attenuating hippocampal necroptosis, and decreasing hippocampal apoptosis, and hippocampal dysplasticity. Male Wistar rats (n = 38) were divided into two groups, sham (n = 6) and cardiac I/R (n = 32). All rats being subjected to the cardiac I/R operation were randomly divided into 4 subgroups (n = 8/group): vehicle, EPO pretreatment, EPO given during ischemia, and EPO given at the onset of reperfusion. The EPO was given at a dosage of 5000 units/kg via intravenous injection. Left ventricle function, oxidative stress, brain mitochondrial function, microglial morphology, hippocampal necroptosis, hippocampal apoptosis, and hippocampal plasticity were measured. EPO administration exerted beneficial anti-oxidative, anti-inflammatory, and anti-apoptotic effects on the brain against cardiac I/R. Giving EPO before cardiac ischemia conferred the greatest neuroprotection against cardiac I/R injury through the attenuation of LV dysfunction, decrease in peripheral and brain oxidative stress, and the attenuation of microglial activation, brain mitochondrial dysfunction, apoptosis, and necroptosis, leading to the improvement of hippocampal dysplasticity under cardiac I/R conditions. EPO pretreatment provided the greatest benefits on brain pathology induced by cardiac I/R.