Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice
Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice
复制标题
金属硫蛋白作为代偿成分可预防小鼠间歇性缺氧诱发的心肌病
DOI：
10.1016/j.taap.2014.03.007
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发表时间：
2014-05-15
影响因子：
3.8
通讯作者：
Cai, Lu
中科院分区：
文献类型：
--
作者：
Yin, Xia;Zhou, Shanshan;Cai, Lu
阻塞性睡眠呼吸暂停（美国）引起慢性间歇性缺氧（1H）诱发心血管疾病，这可能与氧化损伤有关。金属硫蛋白（MT）已被广泛证实是一种内源性的、高度可诱导的抗氧化蛋白。因此，我们测试了氧化应激在USA诱导的心脏损伤中起关键作用和MT保护心脏免受OSA诱导的心肌病的假设。为了模拟美国成年患者中发生的缺氧/复氧事件，将小鼠暴露于IH 3天至8周。IH模式由20.9%O-2/8%O-2F_1 O_2交替循环（每小时30次）组成，在白天F_1 O_2最低点20秒，持续12公顷/天。IH在4周时显著增加心脏重量与胫骨长度的比值，从4到8周心功能下降。IH暴露4周和8周后观察到心脏氧化损伤和纤维化。内源性MT的表达上调3天的IH，但显着下降，在第4和第8周的IH。在支持MT作为一个主要的代偿成分，与心脏MT基因过表达的小鼠和小鼠与全球MT基因缺失完全抵抗，高度敏感，分别慢性IH诱导的心脏效应。这些研究结果表明，慢性1H诱导心肌病的特点是氧化应激介导的心脏损伤和抗氧化剂MT保护心脏免受这种病理和功能的变化。(C)2014爱思唯尔公司All rights reserved.
Obstructive sleep apnea (USA) causes chronic intermittent hypoxia (1H) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in USA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult USA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O-2/8% O-2 F1O2 (30 episodes per hour) with 20s at the nadir F1O2 for 12 ha day during daylight IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic 1H induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes. (C) 2014 Elsevier Inc. All rights reserved.