Puerarin prevents cardiac hypertrophy induced by pressure overload through activation of autophagy
Puerarin prevents cardiac hypertrophy induced by pressure overload through activation of autophagy
复制标题
葛根素通过激活自噬预防压力超负荷引起的心脏肥大
DOI：
10.1016/j.bbrc.2015.07.065
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发表时间：
2015-08-28
影响因子：
3.1
通讯作者：
Chen, Minsheng
中科院分区：
文献类型：
--
作者：
Liu, Bei;Wu, Zhiye;Chen, Minsheng
本研究旨在探讨葛根素对心肌肥厚自噬的影响。大鼠主动脉结扎(AB)后3周内，5‘-单磷酸腺苷激酶(AMPK)活性降低，自噬受到抑制。葛根素治疗AB大鼠3周后，自噬明显恢复。应用葛根素6周可有效抑制心肌细胞肥大和细胞凋亡。在体外实验中，葛根素对异丙肾上腺素诱导的H9c2细胞也有类似的抗肥大和抗凋亡作用。用3-甲基腺嘌呤抑制自噬后，葛根素的保护作用被阻断。进一步的体内研究表明，葛根素显著激活5‘-AMPK的磷酸化，从而抑制哺乳动物雷帕霉素靶蛋白S6核糖体蛋白和4E结合蛋白1的表达。所有这些数据表明，葛根素对心肌细胞肥大和凋亡具有保护作用，部分是通过AMPK/mTOR介导的信号转导恢复自噬。(C)2015 Elsevier Inc.保留所有权利。
This study aimed to explore the effects of puerarin on autophagy in cardiac hypertrophy. Decreased 5'-adenosine monophosphate kinase (AMPK) activity alone with inhibited autophagy could be detected in rats within 3 weeks after aortic banding (AB). Puerarin treatment for 3 weeks in AB rats significantly restored autophagy. Administration of puerarin for 6 weeks effectively restricted cardiomyocyte hypertrophy and apoptosis. In an in vitro study, similar anti-hypertrophy and anti-apoptosis effects of puerarin on isoprenaline-induced H9c2 cells were also observed. After inhibition of autophagy by pretreatment with 3-methyladenine, the protective effects of puerarin were blocked. Further in vivo study demonstrated that puerarin significantly enabled phosphorylation of 5'-AMPK to be activated, subsequently inhibiting expression of the mammalian target of rapamycin (mTOR) target proteins S6 ribosomal protein and 4E-binding protein 1. All these data indicate that puerarin exerts protective effects against cardiomyocyte hypertrophy and apoptosis, partly by restoration of autophagy through AMPK/mTOR-mediated signaling. (C) 2015 Elsevier Inc. All rights reserved.