Kaempferol Protects Pulmonary Vascular Endothelial Function in Rats with High Altitude Pulmonary Hypertension by Regulating RAS System and AMPK/Arg2/eNOS Signaling Pathway

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Natural Product Communications Pub Date : 2024-08-22 DOI:10.1177/1934578x241274896

Xin Xie, Huiru Li, Liangqi Wang, Xiaonan Zhang, Dianxiang Lu, Zhanqiang Li

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Abstract

BackgroundPrevious studies have found that kaempferol can relieve pulmonary hypertension (PH).ObjectiveExplore the protective impact of kaempferol on pulmonary vascular endothelium in rats with high altitude pulmonary hypertension (HAPH).Materials and methodsIn a simulated altitude of 5000 m environment, rats were induced to develop HAPH after continuous intragastric administration of kaempferol (25, 50 and 100 mg·kg−1) and Sildenafil (30 mg·kg−1) for 28 days. Assessment of isolated pulmonary arterial rings in rats and relevant indicators in lung tissue was performed, with the mechanism of action investigated using Western blotting.ResultsKaempferol effectively dilates rat pulmonary arterial rings, with an EC50 of 55.75 μmol/L. L-NAME can effectively counteract the vasodilatory effect of kaempferol. Acetylcholine demonstrated better relaxation of pulmonary arterial rings in HAPH rats after kaempferol intervention. Elastic Van Gieson staining (EVG) and immunohistochemistry (CD31) results indicate that kaempferol can partially protect pulmonary vascular endothelial function in HAPH rats. Western blotting reveals that kaempferol has the ability to regulate the Renin-Angiotensin System (RAS). This leads to a compensatory increase in eNOS expression, upregulation of AMPK activity, and downregulation of eNOS monomer/dimer levels.ConclusionsKaempferol can improve pulmonary vascular endothelial dysfunction caused by chronic hypoxia by upregulating the phosphorylation level of AMPK, regulating the RAS system, and inhibiting eNOS uncoupling, thereby achieving vasodilation and endothelial protection.

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山奈酚通过调节 RAS 系统和 AMPK/Arg2/eNOS 信号通路保护高海拔肺动脉高压大鼠的肺血管内皮功能

背景先前的研究发现山奈酚可以缓解肺动脉高压（PH）.目的探讨山奈酚对高海拔肺动脉高压（HAPH）大鼠肺血管内皮的保护作用.材料和方法在模拟海拔5000 m的环境中，连续胃内给予山奈酚（25、50和100 mg-kg-1）和西地那非（30 mg-kg-1）28天，诱导大鼠发生HAPH。结果山奈酚能有效扩张大鼠肺动脉环，EC50 为 55.75 μmol/L。L-NAME 能有效抵消山奈酚的血管扩张作用。山奈酚干预后，乙酰胆碱能更好地松弛 HAPH 大鼠的肺动脉环。弹性范吉森染色（EVG）和免疫组化（CD31）结果表明，山奈酚能部分保护 HAPH 大鼠的肺血管内皮功能。Western 印迹分析表明，山奈酚具有调节肾素-血管紧张素系统（RAS）的能力。结论山奈酚可以通过上调 AMPK 磷酸化水平、调节 RAS 系统和抑制 eNOS 解偶联来改善慢性缺氧引起的肺血管内皮功能障碍，从而达到扩张血管和保护内皮的目的。

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来源期刊

Natural Product Communications 工程技术-食品科技

CiteScore

3.10

自引率

11.10%

发文量

254

审稿时长

2.7 months

期刊介绍： Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products.