Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart
Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart
复制标题
慢性镁缺乏导致可逆性线粒体通透性转变孔开放并损害大鼠心脏的缺氧耐受性
DOI：
10.1016/j.jphs.2021.12.002
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发表时间：
2022
影响因子：
3.5
通讯作者：
Iesaki Takafumi
中科院分区：
文献类型：
--
作者：
Watanabe Makino;Nakamura Kyoko;Kato Megumi;Okada Takao;Iesaki Takafumi
慢性镁缺乏会诱发和加重各种心血管疾病。我们先前使用朗宁多夫灌流的离体鼠心脏模型研究了慢性镁缺乏引起的心功能下降的潜在机制以及补充镁对这种下降的有效性。在本实验中，我们使用了Langendorff灌流的大鼠离体心模型，显示慢性镁缺乏大鼠(镁缺乏组)的心率(HR)和左心室内压(LVDP)低于镁水平正常的大鼠(正常组)。此外，镁缺乏组由于缺氧/复氧损伤导致的心功能下降明显大于正常组。线粒体通透性转换孔(MPTP)实验显示，缺镁组线粒体膜脆弱，提示缺氧/复氧损伤导致的心功能下降与线粒体功能有关。慢性缺镁大鼠补充镁不仅改善了低镁血症，而且几乎完全恢复了心脏和线粒体的功能。因此，在镁缺乏引起的病理条件下或对于有低镁血症风险的人，积极补充镁可能会抑制某些疾病状态的发展和恶化。
Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.