Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction
Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction
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褪黑素可改善射血分数保留的心力衰竭小鼠模型的心脏功能。
DOI：
10.1016/j.redox.2018.07.007
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发表时间：
2018-09-01
期刊：
影响因子：
11.4
通讯作者：
Yang, Hai-Bo
中科院分区：
文献类型：
--
作者：
Liu, Yuan;Li, Li-Na;Yang, Hai-Bo
褪黑素已被证明可以抑制心肌梗塞诱导的细胞凋亡，但其在射血分数保留的心力衰竭 (HFpEF) 中的作用尚未得到研究。本研究旨在调查褪黑激素是否可以减弱肥胖相关的 HFpEF。雄性小鼠从断奶到 6 个月龄期间喂食高脂饮食 (HFD) 以诱导 HFpEF。 3周后，小鼠口服褪黑激素（50毫克/千克）。补充褪黑激素可显着改善喂食 HFD 的小鼠的舒张功能。褪黑素可减轻肥胖引起的心肌氧化应激和细胞凋亡，并促进脂肪组织分泌 C1q/肿瘤坏死因子相关蛋白 3 (CTRP3)。循环 CTRP3 的消耗在很大程度上消除了褪黑激素介导的心脏保护作用。褪黑激素介导的脂肪细胞来源的 CTRP3 分泌激活了 NF-E2 相关因子 2 (Nrf2)，而这种作用在很大程度上可通过敲低脂肪细胞中的 CTRP3 或心肌细胞中的 Nrf2 来消除。 Nrf2 激活由 miR-200a 介导，miR-200a antagomir 抵消了褪黑激素条件培养基对 Nrf2 表达的影响。我们的结果表明褪黑激素可用于治疗和预防肥胖相关的 HFpEF。
Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity related HFpEF.