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黄芪甲苷通过上调缺氧诱导因子-1α和Notch1/Jagged1信号通路减轻急性心肌梗死大鼠模型的心肌损伤。

Astragaloside attenuates myocardial injury in a rat model of acute myocardial infarction by upregulating hypoxia inducible factor‑1α and Notch1/Jagged1 signaling.

作者信息

Yu Junmin, Zhang Xiaobo, Zhang Yina

机构信息

Department of Geriatrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

出版信息

Mol Med Rep. 2017 Jun;15(6):4015-4020. doi: 10.3892/mmr.2017.6522. Epub 2017 Apr 27.

Abstract

The present study aimed to investigate the mechanisms underlying the cardioprotective effect of Astragaloside against myocardial injury following myocardial infarction (MI) in a rat model. Male Wistar rats were subjected to left anterior descending branch ligation. The rats that survived 24 h (n=18) were randomly and equally assigned to three groups: MI model group, and 2.5 and 10 mg/kg/day Astragaloside group. A further six rats underwent identical surgical procedures without artery ligation, serving as sham controls. Following 28 days of treatment, the left ventricle was harvested for morphological analysis, and mRNA and protein expression levels of hypoxia inducible factor‑1α (HIF‑1α), Notch1 and Jagged1 were measured. Treatment with Astragaloside attenuated pathological changes in the myocardium. Compared with untreated MI rats, rats treated with Astragaloside exhibited significantly increased mRNA expression levels of HIF‑1α, Notch1 and Jagged1 (all P<0.01). HIF‑1α demonstrated a dose‑dependent effect (P<0.05). Astragaloside (10 mg/kg/day) significantly increased HIF‑1α (P<0.05), Notch1 (P<0.01) and Jagged1 (P<0.01) protein expression levels. Additionally, 2.5 mg/kg Astragaloside significantly increased Jagged1 protein expression levels compared with untreated MI rats. Furthermore, there was a dose‑dependent effect of Astragaloside treatment (P<0.01). These findings suggested that the cardioprotective effects of Astragaloside against myocardial injury following MI may involve upregulation of HIF‑α, Notch1 and Jagged1 signaling, implicating these molecules as therapeutic targets for the treatment of MI.

摘要

本研究旨在探讨黄芪甲苷对大鼠心肌梗死(MI)后心肌损伤的心脏保护作用机制。将雄性Wistar大鼠进行左前降支结扎。存活24小时的大鼠(n = 18)被随机且等分为三组:MI模型组、2.5和10mg/kg/天黄芪甲苷组。另外六只大鼠接受相同的手术操作但不进行动脉结扎,作为假手术对照组。治疗28天后,取出左心室进行形态学分析,并检测缺氧诱导因子-1α(HIF-1α)、Notch1和Jagged1的mRNA和蛋白表达水平。黄芪甲苷治疗减轻了心肌的病理变化。与未治疗的MI大鼠相比,用黄芪甲苷治疗的大鼠HIF-1α、Notch1和Jagged1的mRNA表达水平显著升高(均P<0.01)。HIF-1α表现出剂量依赖性效应(P<0.05)。黄芪甲苷(10mg/kg/天)显著提高了HIF-1α(P<0.05)、Notch1(P<0.01)和Jagged1(P<0.01)的蛋白表达水平。此外,与未治疗的MI大鼠相比,2.5mg/kg黄芪甲苷显著提高了Jagged1蛋白表达水平。此外,黄芪甲苷治疗存在剂量依赖性效应(P<0.01)。这些发现表明,黄芪甲苷对MI后心肌损伤的心脏保护作用可能涉及HIF-α、Notch1和Jagged1信号通路的上调,提示这些分子可作为治疗MI的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4087/5436283/09d402ea7634/MMR-15-06-4015-g00.jpg

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