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清达颗粒减弱血管紧张素 II 诱导的心肌肥厚和凋亡,调节 PI3K/AKT 通路。

Qingda granule attenuates angiotensin II-induced cardiac hypertrophy and apoptosis and modulates the PI3K/AKT pathway.

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China; Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.

出版信息

Biomed Pharmacother. 2021 Jan;133:111022. doi: 10.1016/j.biopha.2020.111022. Epub 2020 Dec 1.

DOI:10.1016/j.biopha.2020.111022
PMID:33378940
Abstract

Qingda granule (QDG), simplified from Qingxuan Jiangya Decoction, is a well-known traditional Chinese medicine formula that has been used for decades to treat hypertension. However, the cardioprotective effects of QDG on Ang II-induced hypertension remain unknown. This study aimed to investigate the effects of QDG on hypertension-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Mice were infused with Ang II (500 ng/kg/min) or saline solution as control, then administered oral QDG (1.145 g/kg/day) or saline for two weeks. QDG treatment attenuated the elevation in blood pressure caused by Ang II, as well as the decreased left ventricle ejection fractions and fractional shortening. Moreover, QDG treatment significantly alleviated the Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury, hypertrophy, and apoptosis. In cultured H9C2 cells stimulated with Ang II, QDG partially reversed the increase in cell surface area and number of apoptotic cells, up-regulation of hypertrophy markers ANP and BNP, and activation of caspases-9 and -3. QDG also partially reversed Ang II-induced accumulation of reactive oxygen species (ROS), depolarization of the mitochondrial membrane, release of cytochrome C, up-regulation of Bax, and decrease in levels of p-PI3K, p-AKT, and Bcl-2. These results suggest that QDG can significantly attenuate Ang II-induced hypertension, cardiac hypertrophy and apoptosis, and it may exert these effects in part by suppressing ROS production and activating the PI3K/AKT signaling pathway.

摘要

清达颗粒(QDG),简化自 Qingxuan Jiangya 汤,是一种已被广泛应用数十年的传统中药配方,用于治疗高血压。然而,QDG 对血管紧张素 II(Ang II)诱导的高血压的心脏保护作用尚不清楚。本研究旨在探讨 QDG 对高血压引起的心肌肥大和凋亡的影响,并探索其潜在机制。将小鼠用 Ang II(500ng/kg/min)或生理盐水作为对照进行输注,然后给予口服 QDG(1.145g/kg/天)或生理盐水治疗两周。QDG 治疗可减轻 Ang II 引起的血压升高,以及左心室射血分数和缩短分数的降低。此外,QDG 治疗可显著减轻 Ang II 引起的心脏重量与胫骨长度比值升高,以及心脏损伤、肥大和凋亡。在 Ang II 刺激的 H9C2 细胞中,QDG 部分逆转了细胞表面积和凋亡细胞数量的增加、肥大标志物 ANP 和 BNP 的上调以及半胱氨酸天冬氨酸蛋白酶-9 和 -3 的激活。QDG 还部分逆转了 Ang II 引起的活性氧(ROS)积累、线粒体膜去极化、细胞色素 C 释放、Bax 上调以及 p-PI3K、p-AKT 和 Bcl-2 水平降低。这些结果表明,QDG 可显著减轻 Ang II 引起的高血压、心肌肥大和凋亡,其可能通过抑制 ROS 产生和激活 PI3K/AKT 信号通路发挥这些作用。

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