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清达颗粒通过抑制氧化应激和炎症反应,通过 NOX1 和 NF-κB 途径减轻血管紧张素Ⅱ诱导的高血压肾损伤。

Qingda granule alleviate angiotensin ⅱ-induced hypertensive renal injury by suppressing oxidative stress and inflammation through NOX1 and NF-κB pathways.

机构信息

Academy of Integrative Medicine, 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; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.

出版信息

Biomed Pharmacother. 2022 Sep;153:113407. doi: 10.1016/j.biopha.2022.113407. Epub 2022 Jul 19.

Abstract

Hypertension has become one of the important diseases harmful to human health. In China, Qingda granule (QDG) has been used to treat hypertension for decades. Previous studies by our team have shown that oxidative stress may be one of the pathways through which QDG inhibits hypertension-induced organs injury. However, the specific molecular mechanism of its anti-hypotension and renal oxidative stress response were unclearly. This study investigated QDG's potential protective mechanism against hypertension-induced renal injury. Mice were infused with Angiotensin Ⅱ (Ang Ⅱ, 500 ng/kg/min) or equivalent saline solution (Control) and administered oral QDG (1.145 g/kg/day) or saline for four weeks. QDG treatment mitigated the elevated blood pressure and reduced renal pathological changes induced by Ang Ⅱ. As per the RNA sequencing results, QDG affects oxidative stress signaling. In agreement with these findings, QDG significantly attenuated the Ang Ⅱ-induced increase in Nitrogen oxides 1 (NOX1) and reactive oxygen species and the decrease in superoxide dismutase in renal tissue. Additionally, QDG significantly inhibited Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), and Interleukin 1β (IL-1β) expression in renal tissues and blocked the phosphorylation of P65 (NF-κB subunit) and IκB. These results were confirmed in vitro. Overall, QDG reduced Ang Ⅱ-induced elevated blood pressure and renal injury by inhibiting oxidative stress and inflammation caused by NOX1 and NF-κB pathways. The results of this study provide an experimental basis for the clinical application of QDG, and to open up a new direction for the clinical treatment of hypertension.

摘要

高血压已成为危害人类健康的重要疾病之一。在中国,清达颗粒(QDG)已被用于治疗高血压数十年。本团队之前的研究表明,氧化应激可能是 QDG 抑制高血压引起的器官损伤的途径之一。然而,其抗高血压和肾氧化应激反应的具体分子机制尚不清楚。本研究探讨了 QDG 对高血压肾损伤的潜在保护机制。将小鼠输注血管紧张素Ⅱ(Ang Ⅱ,500ng/kg/min)或等量生理盐水(对照),并给予口服 QDG(1.145g/kg/天)或生理盐水四周。QDG 治疗减轻了 Ang Ⅱ引起的血压升高和肾脏病理变化。根据 RNA 测序结果,QDG 影响氧化应激信号。与这些发现一致,QDG 显著减弱了 Ang Ⅱ诱导的肾组织中氮氧化物 1(NOX1)和活性氧的增加以及超氧化物歧化酶的减少。此外,QDG 显著抑制了肾组织中白细胞介素 6(IL-6)、肿瘤坏死因子 α(TNF-α)和白细胞介素 1β(IL-1β)的表达,并阻断了 P65(NF-κB 亚基)和 IκB 的磷酸化。这些结果在体外得到了证实。总的来说,QDG 通过抑制由 NOX1 和 NF-κB 途径引起的氧化应激和炎症,降低了 Ang Ⅱ引起的血压升高和肾损伤。本研究结果为 QDG 的临床应用提供了实验依据,并为高血压的临床治疗开辟了新的方向。

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