Department of Geriatrics, Nanshi Hospital, Nanyang, 473065, China.
Department of Neurosurgery, The Second People's Hospital of Huai'an, Huai'an, 223002, China.
Chem Biol Interact. 2019 Jan 5;297:44-49. doi: 10.1016/j.cbi.2018.10.016. Epub 2018 Oct 23.
Rutin possesses multiple pharmacological activities, including the cardioprotective effect. The present study aimed to evaluate the protective effects of rutin on hypoxia/reoxygenation (H/R)-induced myocardial injury and its underlying mechanism involved. H9c2 cells were pretreated with 50 μM rutin or combined with 1 μM silent information regulator 1 (SIRT1) inhibitor (EX-527) for 1 h, and subjected to hypoxia for 6 h, followed by reoxygenation for 24 h. SIRT1 expression was detected by qRT-PCR and western blot. The effects of rutin or combined with EX-527 on cell viability, myocardial injury, apoptotic rate, and oxidative stress in H/R-stimulated H9c2 cells were assayed. The results showed that rutin elevated SIRT1 expression in H9c2 cells, as well as H/R-stimulated H9c2 cells. Rutin increased cell viability in H9c2 cells exposed to H/R. H/R stimulation induced myocardial injury, as evidenced by the increased levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and aspartate transaminase (AST), which were abolished in the presence of rutin. Rutin attenuated H/R-induced increase of apoptotic rate and caspase-3 activity in H/R-treated cells. Moreover, H/R-induced decrease in the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and increase in malondialdehyde (MDA) content were reversed by rutin treatment. The presence of EX-527 abolished these protective effects of rutin. In conclusion, rutin protected H9c2 cells against H/R injury through increasing SIRT1 expression. Our findings suggested that rutin might be a potential therapeutic agent for the treatment of myocardial H/R injury.
芦丁具有多种药理活性，包括心脏保护作用。本研究旨在评估芦丁对缺氧/复氧（H/R）诱导的心肌损伤的保护作用及其潜在机制。用 50 μM 芦丁或联合 1 μM 沉默信息调节因子 1（SIRT1）抑制剂（EX-527）预处理 H9c2 细胞 1 h，然后进行 6 h 缺氧，再进行 24 h 复氧。通过 qRT-PCR 和 Western blot 检测 SIRT1 表达。检测芦丁或联合 EX-527 对 H/R 刺激的 H9c2 细胞活力、心肌损伤、凋亡率和氧化应激的影响。结果表明，芦丁可上调 H9c2 细胞和 H/R 刺激的 H9c2 细胞中的 SIRT1 表达。芦丁可增加 H9c2 细胞中 H/R 暴露时的细胞活力。H/R 刺激导致乳酸脱氢酶（LDH）、肌酸激酶-MB（CK-MB）和天冬氨酸转氨酶（AST）水平升高，这在芦丁存在的情况下被消除。芦丁可减轻 H/R 诱导的 H/R 处理细胞凋亡率和半胱天冬酶-3 活性的增加。此外，芦丁可逆转 H/R 诱导的超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）活性降低以及丙二醛（MDA）含量增加。EX-527 的存在消除了芦丁的这些保护作用。总之，芦丁通过增加 SIRT1 表达来保护 H9c2 细胞免受 H/R 损伤。我们的研究结果表明，芦丁可能是治疗心肌 H/R 损伤的潜在治疗剂。
