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清达颗粒对血管紧张素II介导的高血压的全身炎症预防及神经保护作用

Prevention of systemic inflammation and neuroprotective effects of Qingda granules against angiotensin II-mediated hypertension.

作者信息

Zhang Ling, Cai Qiao-Yan, Lin Shan, Jia Bei-Bei, Ye Ren-Zhi, Wang Huai, Bao Li-Ya, Chen You-Qin, Chu Jian-Feng, Peng Jun

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, China/ Chen Keji Academic Thought Heritage Studioc, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian, China.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, China/Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, China/ Chen Keji Academic Thought Heritage Studioc, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian, China.

出版信息

Pak J Pharm Sci. 2020 Jan;33(1(Spec)):469-479.

PMID:32173645
Abstract

Qingxuan Jiangya Decoction (QXJYD), prescribed by academician Ke-ji Chen, has long been used as a Traditional Chinese Medicine formula in blood pressure control and has achieved good clinical outcomes in hypertensive patients. Qingda granules (QDGs), which is a formula simplified from QXJYD, might serve as a novel anti-hypertensive pharmaceutical. However, the functional mechanism of QDGs remains unclear. This study aimed to evaluate the effect of QDGs against the elevation of blood pressure, systemic inflammation and brain injury in Ang II-mediated hypertensive mice. Ang II-mediated hypertensive mice were treated with 28.63mg QDG of per mouse every day. The blood pressure of all mice was measured on days 0, 1, 3, 5, 7, 14 and 28 by using the tail-cuff plethysmograph method. Following 28 days of treatment, the mice were sacrificed and their whole blood and brain tissues were used for analysis. The results showed that QDGs significantly decreased elevated systolic and diastolic blood pressure in Ang II-mediated hypertensive mice while body weight did not change, which demonstrated anti-hypertensive activities of QDGs without obvious toxicity. QDGs significantly attenuated the level of serum cytokines (IL-6, TNF-a) and chemokines (MCP-1, MIP-1a, RANTES) in the Ang II-mediated hypertensive mice. Moreover, pathological staining showed that QDGs significantly ameliorated cerebral histopathology changes, reduced the loss of neurons and activations of astrocytes. Additionally, QDGs inhibited neuronal apoptosis by down-regulation of Bax expression and up-regulation of Bcl-2 expression. These results suggested that QDGs exhibited excellent anti-hypertensive properties by preventing systemic inflammation and providing neuroprotective effects against Ang II-mediated hypertension.

摘要

清眩降压汤(QXJYD)由陈可冀院士所开,长期以来一直作为一种中药配方用于控制血压,并在高血压患者中取得了良好的临床疗效。清达颗粒(QDGs)是由清眩降压汤简化而来的配方,可能成为一种新型的抗高血压药物。然而,清达颗粒的作用机制尚不清楚。本研究旨在评估清达颗粒对血管紧张素II介导的高血压小鼠血压升高、全身炎症和脑损伤的影响。血管紧张素II介导的高血压小鼠每天每只给予28.63mg清达颗粒。在第0、1、3、5、7、14和28天,使用尾套体积描记法测量所有小鼠的血压。治疗28天后,处死小鼠,取其全血和脑组织进行分析。结果表明,清达颗粒可显著降低血管紧张素II介导的高血压小鼠升高的收缩压和舒张压,而体重未发生变化,这表明清达颗粒具有抗高血压活性且无明显毒性。清达颗粒可显著降低血管紧张素II介导的高血压小鼠血清细胞因子(IL-6、TNF-α)和趋化因子(MCP-1、MIP-1α、RANTES)的水平。此外,病理染色显示,清达颗粒可显著改善脑组织病理学变化,减少神经元丢失和星形胶质细胞活化。此外,清达颗粒通过下调Bax表达和上调Bcl-2表达来抑制神经元凋亡。这些结果表明,清达颗粒通过预防全身炎症和对血管紧张素II介导的高血压提供神经保护作用,表现出优异的抗高血压特性。

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