Long-Term Sleep Deprivation-Induced Myocardial Remodeling and Mitochondrial Dysfunction in Mice Were Attenuated by Lipoic Acid and N-Acetylcysteine.
Long-Term Sleep Deprivation-Induced Myocardial Remodeling and Mitochondrial Dysfunction in Mice Were Attenuated by Lipoic Acid and N-Acetylcysteine.
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DOI：
10.3390/ph16010051
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发表时间：
2022-12-29
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影响因子：
--
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中科院分区：
文献类型：
--
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长期睡眠不足对心脏的影响及其潜在机制尚不清楚。本研究旨在探讨慢性睡眠剥夺（CSD）对心脏和线粒体功能的影响，并探索治疗慢性睡眠剥夺引起的心功能障碍的有效药物。我们采用改良的方法诱导小鼠CSD；采用硫辛酸（LA）和n -乙酰半胱氨酸（NAC）治疗CSD小鼠。超声心动图、苏木精-伊红（H&E）染色、天狼星红染色和免疫组化检测心功能和心脏纤维化。测定血清脑利钠肽（BNP）、超氧化物歧化酶（SOD）、微量丙二醛（MDA）和谷胱甘肽（GSH）水平，以确定心血管和氧化应激相关损伤。透射电镜观察线粒体损伤情况。RNA-seq和Western blotting检测相关通路。我们发现左心室射血分数（LVEF）和分数缩短（LVFS）值显著降低，心肌肥厚，线粒体受损，活性氧（ROS）升高，SOD水平降低。心脏组织rna序列分析显示，代谢途径中多种差异表达基因富集。Sirtuin 1 （Sirt1）和谷胱甘肽s -转移酶A3 （Gsta3）可能与csd诱导的心脏和线粒体功能障碍有关。LA和NAC通过调节Sirt1和Gsta3的表达，对CSD小鼠进行ROS药理抑制，有效减轻心脏损伤和线粒体功能障碍。我们的数据有助于理解csd诱导的心脏功能障碍的途径，药理靶向ROS可能是预防csd诱导的心脏损伤的一种策略。
The impact of long-term sleep deprivation on the heart and its underlying mechanisms are poorly understood. The present study aimed to investigate the impact of chronic sleep deprivation (CSD) on the heart and mitochondrial function and explore an effective drug for treating CSD-induced heart dysfunction. We used a modified method to induce CSD in mice; lipoic acid (LA) and N-acetylcysteine (NAC) were used to treat CSD mice. Echocardiography, hematoxylin-eosin (H&E) staining, Sirius red staining, and immunohistochemistry were used to determine heart function and cardiac fibrosis. The serum levels of brain natriuretic peptide (BNP), superoxide Dismutase (SOD), micro malondialdehyde (MDA), and glutathione (GSH) were measured to determine cardiovascular and oxidative stress-related damage. Transmission electron microscopy was used to investigate mitochondrial damage. RNA-seq and Western blotting were used to explore related pathways. We found that the left ventricular ejection fraction (LVEF) and fraction shortening (LVFS) values were significantly decreased and myocardial hypertrophy was induced, accompanied by damaged mitochondria, elevated reactive oxygen species (ROS), and reduced SOD levels. RNA-sequence analysis of the heart tissue showed that various differentially expressed genes in the metabolic pathway were enriched. Sirtuin 1 (Sirt1) and Glutathione S-transferase A3 (Gsta3) may be responsible for CSD-induced heart and mitochondrial dysfunction. Pharmacological inhibition of ROS by treating CSD mice with LA and NAC effectively reduced heart damage and mitochondrial dysfunction by regulating Sirt1 and Gsta3 expression. Our data contribute to understanding the pathways of CSD-induced heart dysfunction, and pharmacological targeting to ROS may represent a strategy to prevent CSD-induced heart damage.
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影响因子：
12.8
作者：
Li S;Ning K;Zhou J;Guo Y;Zhang H;Zhu Y;Zhang L;Jia C;Chen Y;Sol Reinach P;Liu Z;Li W
通讯作者：
Li W
DOI：
10.2174/1874306401105010031
发表时间：
2011
期刊：
The open respiratory medicine journal
影响因子：
--
作者：
Aldabal L;Bahammam AS
通讯作者：
Bahammam AS
影响因子：
3.2
作者：
EL Midaoui, A;Elimadi, A;de Champlain, J
通讯作者：
de Champlain, J
影响因子：
3.3
作者：
Marinho, Priscila M.;Salomon, Tiago B.;Hackenhaar, Fernanda S.
通讯作者：
Hackenhaar, Fernanda S.
急性睡眠不足对健康年轻人心率恢复的影响
影响因子：
2.5
作者：
Cincin, Altug;Sari, Ibrahim;Basaran, Yelda
通讯作者：
Basaran, Yelda