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姜黄素对吡柔比星诱导的心脏毒性的保护作用。

Protective Effects of Against Pirarubicin-Induced Cardiotoxicity.

机构信息

*Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, P. R. China.

‡Department of Cardiology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, P. R. China.

出版信息

Am J Chin Med. 2019;47(5):1075-1097. doi: 10.1142/S0192415X19500551. Epub 2019 Jul 17.

Abstract

Pirarubicin (THP) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. Unfortunately, the clinical effectiveness of THP is limited by its dose-related cardiotoxicity. leaf extract is an extract of the dried leaves of L. (a member of the family, AVLE) that has many positive effects on the cardiovascular system and is widely consumed as tea in China. In this study we established a cardiactoxicity rat model, which showed that pretreatment with AVLE attenuated THP-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. AVLE also significantly reduced serum levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (CTnT), and lactate dehydrogenase (LDH); and increased serum superoxide dismutase (SOD) levels. Treatment with AVLE or dexrazoxane (DZR) resulted in an increase Cytochrome C (cytc) in the mitochondria and reduced Cytc and cleaved-caspase-3 levels () in cytoplasm. We also found that AVLE significantly reduced voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD) mRNA expression (). Furthermore, AVLE appeared to exert therapeutic effects in a dose-dependent manner. Our study suggests the anti-oxidant and anti-apoptotic properties of AVLE may be responsible for the observed cardioprotective effects.

摘要

盐酸吡柔比星(THP)是一种蒽环类抗生素,常用于治疗多种人类癌症。不幸的是,THP 的临床疗效受到其剂量相关的心脏毒性的限制。艾叶提取物是艾草(菊科蒿属,AVLE)的干叶提取物,对心血管系统有许多积极影响,在中国广泛作为茶饮用。在本研究中,我们建立了心脏毒性大鼠模型,结果表明,AVLE 预处理可减轻 THP 诱导的心肌组织病理学损伤、心电图异常和心功能障碍。AVLE 还显著降低了血清丙二醛(MDA)、脑钠肽(BNP)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白(CTnT)和乳酸脱氢酶(LDH)水平;并增加了血清超氧化物歧化酶(SOD)水平。AVLE 或右雷佐生(DZR)治疗导致线粒体 Cytc 增加,细胞质 Cytc 和裂解 caspase-3 水平()降低。我们还发现 AVLE 显著降低电压依赖性阴离子通道 1(VDAC1)、腺苷核苷酸转运蛋白 1(ANT1)和亲环素 D(CYPD)mRNA 表达()。此外,AVLE 似乎以剂量依赖的方式发挥治疗作用。我们的研究表明,AVLE 的抗氧化和抗细胞凋亡特性可能是其观察到的心脏保护作用的原因。

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