Apocynin 防止心肌神经生长因子减少，有助于改善心肌细胞凋亡和衰竭,Clinical and Experimental Pharmacology and Physiology

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Apocynin 防止心肌神经生长因子减少，有助于改善心肌细胞凋亡和衰竭
Clinical and Experimental Pharmacology and Physiology ( IF 2.4 ) Pub Date : 2021-03-01 , DOI: 10.1111/1440-1681.13465
Xi Jie _{1,

2} , Hong Yang _{1,

2} , Ke Wang _{1,

2} , Zong-Feng Zhu _{1,

2} , Jia-Pu Wang ₃ , Li-Guo Yang _{1,

2} , Zi-Jian Yang ₃ , Xiao-Juan Zhang _{2,

3} , Ai-Ling Wang _{1,

2} , Lu Li _{1,

2} , Rui-Fang Chi _{1,

2} , Fu-Zhong Qin _{1,

2} , Bao Li _{1,

2} , Bianai Fan ₄

Affiliation

减少的神经生长因子 (NGF) 与心力衰竭 (HF) 中的心脏交感神经去神经支配有关，心力衰竭 (HF) 的特征是氧化应激增加。夹竹桃麻素被认为是一种抗氧化剂，可抑制 NADPH 氧化酶活性并改善活性氧清除。然而，尚不清楚夹竹桃素是否能防止心肌 NGF 减少，从而改善心衰患者的心功能。在这项研究中，我们检验了夹竹桃素可防止心肌 NGF 减少，从而改善心肌细胞凋亡和衰竭的假设。患有心肌梗塞 (MI) 或假手术的兔子被随机分配接受夹竹桃素或安慰剂治疗 4 周。MI 兔表现出左心室 (LV) 功能障碍和氧化应激升高，远端非梗塞心肌中还原型谷胱甘肽与氧化型谷胱甘肽比值降低，4-羟基壬烯醛表达升高，以及 NGF 和 NGF 受体酪氨酸激酶 A (TrKA) 表达降低都证明了这一点。夹竹桃麻素治疗改善了左心室功能障碍，减少了氧化应激，防止了 NGF 和 TrKA 表达的降低，并减少了 MI 后的心肌细胞凋亡。在培养的 H9C2 心肌细胞中，缺氧或过氧化氢降低 NGF 表达，夹竹桃素使缺氧诱导的 NGF 减少正常化。重组 NGF 减弱缺氧诱导的细胞凋亡。Apocynin 阻止缺氧诱导的细胞凋亡，NGF 受体 TrKA 抑制剂 K252a 消除了 apocynin 对细胞凋亡的抑制作用。我们得出结论，夹竹桃素可防止心肌 NGF 减少，导致心肌细胞凋亡减弱和 LV 重构和 MI 后 HF 功能障碍。这些发现表明，通过抑制氧化应激来防止 NGF 减少的策略可能对改善 HF 中的 LV 功能障碍具有价值。

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Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced‐to‐oxidized glutathione ratio and an increased 4‐hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non‐infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia‐induced reduction of NGF. Recombinant NGF attenuated hypoxia‐induced apoptosis. Apocynin prevented hypoxia‐induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.

更新日期：2021-04-02

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