Tsibulnikov Sergey Y, Maslov Leonid N, Naryzhnaya Natalia V, Ma Huijie, Lishmanov Yury B, Oeltgen Peter R, Garlid Keith
Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center, Tomsk 634012, Russia.
Gen Physiol Biophys. 2018 Sep;37(5):537-547. doi: 10.4149/gpb_2018013.
It was established that adaptation to chronic continuous normobaric hypoxia (CCNH) increases cardiac tolerance to ischemia and reperfusion. It was performed coronary artery occlusion (20 min) and reperfusion (3 h) in Wistar rats. CCNH promoted a decrease in the infarct size/area at risk ratio in 2-fold. CCNH promoted an increase in the nitrite/nitrate levels in blood serum and myocardium. Pretreatment with protein kinase C (PKC) inhibitor chelerythrine, NO-synthase (NOS) inhibitor L-NAME, iNOS inhibitor S-methylisothiourea, KATP channel blocker glibenclamide, mitoKATP channel blocker 5-hydroxydecanoic acid abolished the infarct-reducing effect of CCNH. The non-selective tyrosine kinase inhibitor genistein attenuated but not eliminated infarct-sparing effect of CCNH. The nNOS inhibitor 7-nitroindazole, sarcKATP channel blocker HMR 1098, MPT pore inhibitor atractyloside, PI3 kinase inhibitor wortmannin did not reverse infarct-limiting effect of CCNH. It was concluded that infarct-reducing effect of CCNH is mediated via PKC, iNOS activation and mitoKATP channel opening. While nNOS, PI3 kinase, sarcKATP channel, MPT pore are not involved in the development of CCNH-induced cardiac tolerance to impact of ischemia-reperfusion.
已证实，适应慢性持续性常压缺氧（CCNH）可增强心脏对缺血和再灌注的耐受性。在Wistar大鼠中进行冠状动脉闭塞（20分钟）和再灌注（3小时）。CCNH使梗死面积与危险面积之比降低了2倍。CCNH使血清和心肌中的亚硝酸盐/硝酸盐水平升高。用蛋白激酶C（PKC）抑制剂白屈菜红碱、一氧化氮合酶（NOS）抑制剂L-NAME、诱导型一氧化氮合酶（iNOS）抑制剂S-甲基异硫脲、钾离子通道（KATP）阻断剂格列本脲、线粒体KATP通道阻断剂5-羟基癸酸进行预处理，可消除CCNH的梗死面积减小效应。非选择性酪氨酸激酶抑制剂染料木黄酮减弱但未消除CCNH的梗死面积减小效应。神经元型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑、肌浆网KATP通道阻断剂HMR 1098、线粒体通透性转换孔（MPT）抑制剂苍术苷、磷脂酰肌醇-3激酶（PI3激酶）抑制剂渥曼青霉素并未逆转CCNH的梗死面积限制效应。得出的结论是，CCNH的梗死面积减小效应是通过PKC、iNOS激活和线粒体KATP通道开放介导的。而nNOS、PI3激酶、肌浆网KATP通道、MPT孔不参与CCNH诱导的心脏对缺血再灌注影响的耐受性的形成。
