Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models
Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models
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虎杖甙可防止去氧肾上腺素诱导的新生小鼠心肌细胞和压力超负荷小鼠模型的肥大。
DOI：
10.1016/j.ejphar.2014.11.012
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发表时间：
2015-01-05
影响因子：
5
通讯作者：
Liu, Jie
中科院分区：
文献类型：
--
作者：
Dong, Ming;Ding, Wenwen;Liu, Jie
白藜芦醇甙白藜芦醇苷（PD）可能对心肌肥厚有保护作用。因此，目前的研究集中在PD的抗心肌细胞肥大的作用，并在体内从心肌肥厚的发展到心力衰竭的潜在机制。实验进行了培养的新生大鼠，心室肌细胞以及成年小鼠进行横向主动脉缩窄（TAC）。用苯丙氨酸处理心肌细胞3天产生显著的肥大效应，细胞表面积和心钠素（ANP）蛋白表达显著增加。PD以浓度依赖性方式减弱这些作用，在50 μ M浓度下完全抑制肥大。苯丙氨酸增加ROCK活性，以及细胞内活性氧的产生和脂质过氧化。氧化剂DTDP同样增加Rho激酶（ROCK）的活性，并诱导肥大性重塑。PD治疗抑制苯肾上腺素诱导的氧化应激，从而抑制心肌细胞中的ROCK激活。在接受13周TAC的小鼠中证实了肥大性重塑和心力衰竭。ROCK信号通路的上调在TAC小鼠中也是明显的。PD治疗显著减弱增加的ROCK活性，与显着减少肥大反应和改善心功能。我们的研究结果表明，一个强大的抗肥厚重塑作用的虎杖苷，这是通过抑制活性氧依赖性ROCK激活介导的。（C）2014年爱思唯尔。All rights reserved.
Recent evidence suggests that polydatin (PD), a resveratrol glucoside, may have beneficial actions on the cardiac hypertrophy. Therefore, the current study focused on the underlying mechanism of the PD antihypertrophic effect in cultured cardiomyocytes and in progression from cardiac hypertrophy to heart failure in vivo.Experiments were performed on cultured neonatal rat, ventricular myocytes as well as adult mice subjected to transverse aortic constriction (TAC). Treatment of carcliomyocytes with phenylephrine for three days produced a marked hypertrophic effect as evidenced by significantly increased cell surface area and atrial natriurctic peptide (ANP) protein expression. These effects were attenuated by PD in a concentration dependent manner with a complete inhibition of hypertrophy at the concentration of 50 mu M. Phenylephrine increased ROCK activity, as well as intracellular reactive oxygen species production and lipid peroxidation. The oxidizing agent DTDP similarly increased Rho kinase (ROCK) activity and induced hypertrophic remodeling. PD treatment inhibited phenylephrine-induced oxidative stress and consequently suppressed ROCK activation in cardiomyocytes. Hypertrophic remodeling and heart failure were demonstrated in mice subjected to 13 weeks of TAC. Upregulation of ROCK signaling pathway was also evident in TAC mice. PD treatment significantly attenuated the increased ROCK activity, associated with a markedly reduced hypertrophic response and improved cardiac function.Our results demonstrated a robust anti-hypertrophic remodeling effect of polydatin, which is mediated by inhibition of reactive oxygen species dependent ROCK activation. (C)2014 Elsevier By. All rights reserved.