Age-related changes in mineralocorticoid receptors in rat hearts
Age-related changes in mineralocorticoid receptors in rat hearts
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DOI：
10.3892/mmr.2020.11260
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发表时间：
2020-09-01
影响因子：
3.4
通讯作者：
Tu, Ling
中科院分区：
文献类型：
--
作者：
Hu, Danli;Dong, Ruolan;Tu, Ling
在心血管系统中，肾素-血管紧张素-醛固酮系统（RAAS）的年龄相关改变已被报道；然而，RAAS成分矿物皮质激素受体（MR）的详细机制尚未阐明。本研究旨在探讨MR与大鼠心脏衰老之间的关系，以及氧化应激和线粒体异常在衰老过程中的调节作用。对3月龄雄性Sprague-Dawley大鼠（幼鼠）和24月龄雄性Sprague-Dawley大鼠（老龄大鼠）心脏MR表达进行体内检测。此外，在体外，用特异性MR拮抗剂epleenone处理H9C2细胞，以研究抑制肌细胞衰老过程的分子机制。结果表明，MR在24月龄大鼠心脏中的表达明显高于3月龄大鼠心脏。这些变化伴随着p53表达增加，过氧化物酶体增殖物激活受体γ辅助激活因子-1 α表达减少，电镜检查线粒体更新减少，氧化应激增加，超氧化物歧化酶减少。体外，通过观察p16、p21和p53的表达水平以及活性氧（ROS）的过度积累，可以发现MR的选择性拮抗作用部分阻断h2o2诱导的心肌衰老。这些结果表明，MR表达增加可能通过线粒体损伤、ROS积累增加和氧化还原状态不平衡来驱动年龄相关的心功能障碍。
Age-related alterations in the renin-angiotensin-aldosterone system (RAAS) have been reported in the cardiovascular system; however, the detailed mechanism of the RAAS component mineralocorticoid receptors (MR) has not been elucidated. The present study aimed to investigate the associations between MR and cardiac aging in rats, as well as the regulatory effects of oxidative stress and mitochondrial abnormalities in the aging process. MR expression in the hearts of male Sprague-Dawley rats aged 3 months (young rats) and 24 months (old rats) was evaluatedin vivo. In addition,in vitro, H9C2 cells were treated with a specific MR antagonist, eplerenone, in order to investigate the molecular mechanism underlying the inhibition of myocyte aging process. The results demonstrated that MR expression was significantly higher in 24-month-old rat hearts compared with in 3-month-old rat hearts. These changes were accompanied by increased p53 expression, decreased peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression, decreased mitochondrial renewal as assessed by electron microscopy, increased oxidative stress and decreased superoxide dismutase.In vitro, selective antagonism of MR partially blocked H2O2-induced myocardial aging as assessed by p16, p21 and p53 expression levels and excessive reactive oxygen species (ROS) accumulation. These results indicated that increased MR expression may drive age-related cardiac dysfunction via mitochondrial damage, increased ROS accumulation and an imbalanced redox state.