Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling
Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling
复制标题
木犀草素通过激活 Akt/Nrf2 信号传导减轻高胆固醇血症大鼠的心脏缺血/再灌注损伤
DOI：
10.1007/s00210-018-1496-2
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发表时间：
2018-07-01
影响因子：
3.6
通讯作者：
Qian, Ling-Bo
中科院分区：
文献类型：
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作者：
Yang, Jin-Ting;Wang, Jue;Qian, Ling-Bo
高胆固醇血症中的心肌缺血/再灌注（I/R）损伤与氧化应激相关，而已知毛地黄黄酮通过激活Akt/核因子红细胞-2相关因子2（Nrf 2）信号传导来降低氧化应激并减轻心脏I/R损伤。在这里，我们研究了毛地黄黄酮预处理是否通过激活Akt/Nrf 2信号通路减少高胆固醇血症大鼠心肌I/R损伤。高胆固醇血症大鼠用2%胆固醇饲料喂养8周。木犀草素（100 mg/kg/天，i.g.）或LY 294002给药最后2周。然后分离心脏，并进行30分钟的全脑缺血，然后再灌注120分钟。毛地黄黄酮预处理可显著改善高胆固醇血症I/R大鼠再灌注期间的左室功能，增加心肌组织活力，降低冠脉乳酸脱氢酶释放和心肌丙二醛水平，上调p-Akt和p-GSK 3 β表达，抑制Fyn核转位，激活Nrf 2功能。LY 294002可明显减弱木樨草素的上述改善作用。Ca 2+诱导的线粒体通透性转换孔（mPTP）开放和线粒体内膜电位降低显着抑制从木犀草素处理的高胆固醇血症大鼠，这是衰减LY 294002的心室肌细胞。这些结果表明，毛地黄黄酮保护高胆固醇血症的心脏免受I/R损伤，由于Akt介导的Nrf 2抗氧化功能的上调和mPTP的抑制。
Myocardial ischemia/reperfusion (I/R) injury in hypercholesterolemia is associated with oxidative stress, while luteolin is known to reduce oxidative stress by activating Akt/nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and alleviate cardiac I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in hypercholesterolemic rats by activating Akt/Nrf2 signaling. Hypercholesterolemic rats were produced by 2% cholesterol diet for 8 weeks. Luteolin (100 mg/kg/day, i.g.) or LY294002 was administered for the last 2 weeks. The hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. Pretreatment with luteolin significantly improved left ventricular function throughout reperfusion, increased cardiac tissue viability, reduced coronary lactate dehydrogenase release and the myocardial malondialdehyde level, upregulated p-Akt and p-GSK3β expressions, inhibited nuclear translocation of Fyn, and activated Nrf2 function in hypercholesterolemic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by LY294002. Ca2+-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated hypercholesterolemic rats, which were attenuated by LY294002. These results indicate that luteolin protects the hypercholesterolemic heart against I/R injury due to upregulation of Akt-mediated Nrf2 antioxidative function and inhibition of mPTP.