首页> 外文期刊>American Journal of Physiology >Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.
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Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.

机译:褪黑素通过抑制线粒体通透性过渡孔的开放来保护心脏免受缺血再灌注损伤。

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Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening. Isolated perfused rat hearts were subjected to global ischemia and reperfusion in the presence or absence of melatonin in a Langerdoff apparatus. Melatonin treatment significantly improves the functional recovery of Langerdoff hearts on reperfusion, reduces the infarct size, and decreases necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria isolated from melatonin-treated hearts are less sensitive than mitochondria from reperfused hearts to MPTP opening as demonstrated by their higher resistance to Ca(2+). Similar results were obtained following treatment of ischemic-reperfused rat heart with cyclosporine A, a known inhibitor of MPTP opening. In addition, melatonin prevents mitochondrial NAD(+) release and mitochondrial cytochrome c release and, as previously shown, cardiolipin oxidation associated with ischemia-reperfusion. Together, these results demonstrate that melatonin protects heart from reperfusion injury by inhibiting MPTP opening, probably via prevention of cardiolipin peroxidation.
机译:褪黑素是一种著名的抗氧化剂,已被证明可以防止缺血再灌注心肌损伤。线粒体通透性转换孔(MPTP)的打开是缺血再灌注过程中发生的心肌细胞死亡的重要事件,因此可能是心脏保护的靶标。在本研究中,我们测试了褪黑激素可以通过抑制MPTP的开放来保护心脏免受缺血再灌注损伤的假说。在存在或不存在褪黑激素的情况下,在Langerdoff装置中对孤立的灌流大鼠心脏进行整体缺血和再灌注。褪黑素治疗可显着改善再灌注时Langerdoff心脏的功能恢复,减小梗塞面积并减少坏死性损伤(如乳酸脱氢酶释放减少所显示)。从褪黑素治疗的心脏分离的线粒体不如从再灌注的心脏到MPTP开放的线粒体敏感,这表现为它们对Ca(2+)的更高抗性。用环孢霉素A(一种已知的MPTP开放抑制剂)治疗缺血再灌注大鼠心脏后,可获得类似的结果。此外,褪黑素可防止线粒体NAD(+)释放和线粒体细胞色素c释放,并且如先前所示,可防止与缺血再灌注相关的心磷脂氧化。总之,这些结果表明褪黑激素可能通过防止心磷脂过氧化而抑制MPTP的开放,从而保护心脏免受再灌注损伤。

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