中药六味地黄丸通过减少坏死机制改善缺血缺氧诱导的心脏损伤和重塑

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Yi‐Yue Zhang, Can Tang, Ya‐Qi Dou, Xiu‐Ju Luo, Jian Pu, Jun Peng
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引用次数: 0

摘要

六味地黄丸(LQHXDW)是一种中药,常用于治疗心悸、胸闷、胸痛和气短等症状。然而,它在减轻缺血或缺氧引起的心脏损伤和重塑方面的潜力及其确切机制仍不清楚。本研究旨在探讨 LQHXDW 在体内和体外对缺血或缺氧诱导的心脏损伤和重构的影响,并阐明其潜在机制。小鼠心脏缺血 14 天后出现明显的心肌损伤和心脏重塑,并伴有心功能减退;LQHXDW 的存在可逆转这些现象。在缺氧条件下培养的心肌细胞中,与 LQHXDW 一起孵育可提高细胞活力并减少乳酸脱氢酶的释放。从机理上讲,LQHXDW对缺血小鼠心脏和缺氧培养心肌细胞中RIPK1、RIPK3和MLKL的磷酸化水平以及氧化应激均有抑制作用。通过超高效液相色谱-四极杆飞行时间质谱法、网络药理学和细胞热转移分析等方法,我们发现咖啡酸苯乙酯和异桔梗素是 LQHXDW 中潜在的能对抗坏死的活性化合物。基于这些观察结果,我们得出结论:LQHXDW 通过抑制依赖于 RIPK1/RIPK3/MLKL 通路的坏死和氧化应激,保护心脏免受缺血或缺氧引起的心脏损伤和重塑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Chinese Herbal Medicine Li Qi Huo Xue Di Wan Ameliorates Ischemia or Hypoxia‐Induced Cardiac Injury and Remodeling in the Heart Through a Mechanism Involving Reduction of Necroptosis
Li Qi Huo Xue Di Wan (LQHXDW), a Chinese herbal medicine, is commonly used to treat symptoms such as palpitations, chest tightness, chest pain, and shortness of breath. However, its potential to reduce ischemia or hypoxia‐induced cardiac injury and remodeling, along with the precise mechanisms involved, remains unclear. This study aims to investigate the effects of LQHXDW on cardiac injury and remodeling induced by ischemia or hypoxia, both in vivo and in vitro, and to elucidate the underlying mechanisms. The mouse heart was subjected to ischemia for 14 days, showing evident myocardial injury and notable cardiac remodeling, accompanied by a reduction in cardiac function; these phenomena were reversed in the presence of LQHXDW. In the cultured cardiomyocyte exposed to hypoxia, incubation with LQHXDW increased the cell viability and reduced lactate dehydrogenase release. Mechanistically, LQHXDW exerted inhibitory effect on the phosphorylation levels of RIPK1, RIPK3, and MLKL as well as oxidative stress in the mice hearts suffered ischemia and the cultured cardiomyocytes exposed to hypoxia. Using the methods of ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry, network pharmacology, and cellular thermal shift assay, phenethyl caffeate and isoliquiritigenin were identified as the potential active compounds in LQHXDW that counteract necroptosis. Based on these observations, we conclude that LQHXDW protects the heart against ischemia or hypoxia‐induced cardiac injury and remodeling through suppression of the RIPK1/RIPK3/MLKL pathway‐dependent necroptosis and oxidative stress.
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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