Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload‐induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction (TAC). Male C57BL/6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8‐week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α‐myosin heavy chain, downregulated the expression level of β‐myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator‐activated receptor‐gamma co‐activator‐1 beta (PGC‐1β) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II‐induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC‐1β using small interfering RNA. In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC‐1β.

中文翻译：

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褪黑素通过激活PGC-1β来预防由横向主动脉缩窄引起的病理性心肌肥大：体内和体外研究

褪黑素是松果体分泌的一种昼夜节律分子，对甲状腺机能亢进，慢性缺氧和异丙肾上腺素引起的心脏肥大具有保护作用。然而，它对压力超负荷引起的心脏肥大及其潜在机制的作用仍然难以捉摸。在这项研究中，我们研究了褪黑激素对由横向主动脉缩窄（TAC）诱发的病理性心肌肥大的药理作用。雄性C57BL / 6小鼠在第0天接受TAC或假手术，然后用褪黑激素（20 mg / kg /天，通过饮用水）治疗4或8周。褪黑激素显着​​提高了TAC手术后的8周生存率。褪黑素治疗8周可明显改善心脏肥大。与TAC组相比，褪黑素治疗4周和8周均能减少肺部充血，上调α-肌球蛋白重链的表达水平，下调β-肌球蛋白重链和心钠素的表达水平，并减轻心脏纤维化程度。此外，褪黑激素治疗减缓了因压力超负荷引起的心脏收缩功能的恶化。褪黑激素的这些作用伴随着过氧化物酶体增殖物激活的受体-γ共激活因子-1 beta（PGC-1β）的表达显着上调和氧化应激的抑制。体外研究表明，褪黑激素还可以预防血管紧张素II诱导的心肌肥大和氧化应激，通过使用小分子干扰RNA抑制PGC-1β的表达，褪黑激素就可以基本消除。总之，