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黄芪甲苷IV调节PI3K/Akt/HO-1信号通路并抑制缺氧复氧诱导的H9c2心肌细胞损伤。

Astragaloside IV Regulates the PI3K/Akt/HO-1 Signaling Pathway and Inhibits H9c2 Cardiomyocyte Injury Induced by Hypoxia-Reoxygenation.

作者信息

Yang Ping, Zhou Yuping, Xia Qing, Yao Lipeng, Chang Xiuchun

机构信息

Ningbo College of Health Sciences.

The Affiliated Hospital of Medical School of Ningbo University.

出版信息

Biol Pharm Bull. 2019 May 1;42(5):721-727. doi: 10.1248/bpb.b18-00854. Epub 2019 Mar 13.

Abstract

Astragaloside IV (AS-IV) is one of the main pharmacologically active compounds found in Astragalus membranaceus. AS-IV has protective effects against ischemia-reperfusion injury (IRI), but its mechanism of action has not yet been determined. This study aims to investigate the effect of AS-IV on IRI and its effect on the phosphadylinositol 3-kinase (PI3K)/Akt/heme oxygenase (HO-1) signaling pathway through in vitro experiments. Firstly, a cell culture model of myocardiocyte hypoxia-reoxygenation (H/R) injury was replicated. After AS-IV treatment, cell viability, reactive oxygen species (ROS) levels, as well as the content or activity of the cellular factors lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), were measured to evaluate the effect of treatment with AS-IV. The effect of AS-IV on HO-1 protein expression and nuclear factor E2-related factor 2 (Nrf2) and Bach1 protein expression was determined by Western blotting. Finally, a reversal of the effect of AS-IV treatment was observed following co-incubation with a PI3K inhibitor. Our results show that AS-IV has good protective effect on H/R injury and has anti-oxidative stress and anti-inflammatory effects. It can regulate the expression of Nrf2 and Bach1 proteins in the nucleus and promote the expression of HO-1 protein, while a PI3K inhibitor can partially reverse the above effects. This study suggests that the PI3K/Akt/HO-1 signaling pathway may be a key signaling pathway for the anti-IRI effect of AS-IV.

摘要

黄芪甲苷IV(AS-IV)是黄芪中发现的主要药理活性化合物之一。AS-IV对缺血再灌注损伤(IRI)具有保护作用,但其作用机制尚未确定。本研究旨在通过体外实验探讨AS-IV对IRI的影响及其对磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/血红素加氧酶(HO-1)信号通路的影响。首先,复制心肌细胞缺氧复氧(H/R)损伤的细胞培养模型。AS-IV处理后,检测细胞活力、活性氧(ROS)水平以及细胞因子乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)的含量或活性,以评估AS-IV处理的效果。通过蛋白质印迹法测定AS-IV对HO-1蛋白表达以及核因子E2相关因子2(Nrf2)和Bach1蛋白表达的影响。最后,在与PI3K抑制剂共同孵育后观察到AS-IV处理效果的逆转。我们的结果表明,AS-IV对H/R损伤具有良好的保护作用,具有抗氧化应激和抗炎作用。它可以调节细胞核中Nrf2和Bach1蛋白的表达,促进HO-1蛋白的表达,而PI3K抑制剂可以部分逆转上述作用。本研究表明,PI3K/Akt/HO-1信号通路可能是AS-IV抗IRI作用的关键信号通路。

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