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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Galectin-3 inhibition attenuates doxorubicin-induced cardiac dysfunction by upregulating the expression of peroxiredoxin-4
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Galectin-3 inhibition attenuates doxorubicin-induced cardiac dysfunction by upregulating the expression of peroxiredoxin-4

机译:通过上调过洛氮毒素-4的表达,Galectin-3抑制抑制了多柔比蛋白诱导的心脏功能障碍

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摘要

Doxorubicin (DOX) is a highly efficient chemotherapeutic drug limited by its cardiotoxicity. Galectin-3 (Gal-3) overexpression is associated with several cardiovascular diseases. In this study, the in vivo models of DOX-treated rats and the in vitro model of DOX-treated H9C2 cells were used. DOX induced cardiac injury and dysfunction accompanied with the upregulation of Gal-3 at the end of the experiment, while inhibition of Gal-3 with modified citrus pectin (MCP) exhibited a dramatic improvement in cardiac function of the DOX-treated rats, as manifested by increased left ventricular systolic pressure and +/- dp/dt(max) and decreased left ventricular end-diastolic pressure. The plasma levels of myocardial injury markers such as lactate dehydrogenase, creatine kinase, creatine kinase-MB, and cardiac troponin I were decreased after MCP treatment. In parallel, MCP attenuated myocardial tissue markers of oxidative stress such as hydrogen peroxide and malondialdehyde restored the activities of superoxide dismutase, catalase, and glutathione peroxidase and upregulated antioxidant peroxiredoxin-4 (Prx-4). To further verify the role of Prx-4, it was downregulated by siRNA-mediated knockdown in H9C2 cells. MCP could not reverse DOX-induced oxidative stress in Prx-4-knock-down cells. In conclusion, Gal-3 mediated DOX-induced cardiotoxicity and Gal-3 inhibition attenuated DOX-induced cardiac dysfunction by upregulating the expression of Prx-4 to reduce myocardial oxidative stress.
机译:阿霉素(DOX)是一种高效的化疗药物,其心脏毒性有限。Galectin-3(Gal-3)过表达与多种心血管疾病相关。本研究采用了DOX处理的大鼠体内模型和DOX处理的H9C2细胞体外模型。在实验结束时,DOX诱导的心脏损伤和功能障碍伴随着Gal-3的上调,而改性柑橘果胶(MCP)对Gal-3的抑制表现出DOX治疗大鼠心脏功能的显著改善,表现为左室收缩压和+/-dp/dt(max)增加,左室舒张末压降低。MCP治疗后,血浆乳酸脱氢酶、肌酸激酶、肌酸激酶MB和心肌肌钙蛋白I等心肌损伤标志物水平降低。同时,MCP减弱了过氧化氢和丙二醛等氧化应激心肌组织标志物,恢复了超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性,并上调了抗氧化剂过氧化物酶-4(Prx-4)。为了进一步验证Prx-4的作用,它在H9C2细胞中被siRNA介导的敲除下调。MCP不能逆转DOX诱导的Prx-4敲除细胞氧化应激。总之,Gal-3介导的DOX诱导的心脏毒性和Gal-3抑制通过上调Prx-4的表达来减轻心肌氧化应激,从而减轻DOX诱导的心功能不全。

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