Let-7g is involved in doxorubicin induced myocardial injury

Let-7g is involved in doxorubicin induced myocardial injury
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DOI:
10.1016/j.etap.2011.12.023
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发表时间:
2012-03-01
影响因子:
4.3
通讯作者:
Wei, Xuetao
Wei, Xuetao
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Fu, Jun;Peng, Cike;Wei, Xuetao

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目的:为了探讨let-7 g(miRNA)是否参与了阿霉素的心脏毒性作用,采用多柔比星(Doxorubicin,Doxin)对大鼠心脏进行了不同剂量的干预。测量心率、脉压和血浆心肌肌钙蛋白T浓度。将原代培养的心肌细胞与浓度递增的DOX(0 μ mol/1、0.004 μ mol/1、0.02 μ mol/1、0.1 μ mol/1、0.5 μ mol/1)孵育24小时。测量细胞活力和搏动频率。结果:与对照组相比,DOX组大鼠注射DOX后心率减慢,脉压增加(p < 0.05)。18 mg/kg组cTnT浓度显著升高。18 mg/kg组和阿霉素组let-7 g含量均显著降低(p < 0.05)。结论:心肌损伤模型中let-7 g表达下调,提示let-7 g可能在心脏疾病的发生发展中起重要作用。(C)出版社:Elsevier B. V.
Objectives: To investigate whether let-7g (miRNA) was involved in doxorubicin-induced cardiotoxicity.Methods: Rats were treated with doxorubicin at increasing doses (0 mg/kg, 6 mg/kg, 12 mg/kg, 18 mg/kg). Heart rate, pulse pressure and plasma cardiac troponin T concentrations were measured. Primary cultured myocardial cells were incubated with DOX at increasing concentrations (0 mu mol/1, 0.004 mu mol/1, 0.02 mu mol/1, 0.1 mu mol/1, 0.5 mu mol/1) for 24h. Cellular viability and the beat frequency were measured. For both rats and cultured cells, miRNA content was measured by real-time reverse-transcription PCR.Results: All DOX-treated rats had a decrease in heart rate, an increase in pulse pressure compared with control group after injections (p < 0.05). Concentration of cTnT was increased significantly in 18 mg/kg group. Content of let-7g decreased significantly (p < 0.05) in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro.Conclusions: The down regulation of let-7g in the myocardial-injury model suggests that let-7g may play an important role in the development of cardiac disease. (C) 2012 Published by Elsevier B.V.