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红景天苷通过增强 NO 生物利用度和调节精氨酸代谢来缓解肺动脉高压。

Salidroside enhances NO bioavailability and modulates arginine metabolism to alleviate pulmonary arterial hypertension.

机构信息

Zhejiang Cancer Hospital, Hangzhou Institute of Medicine and Cancer (HIM), Chinese Academy of Sciences, 1# Banshan east Road, Gongshu District, Hangzhou, CN 310022, Zhejiang, China.

Wannan Medical College, Wuhu, 241000, Anhui, China.

出版信息

Eur J Med Res. 2024 Aug 17;29(1):423. doi: 10.1186/s40001-024-02016-x.

DOI:10.1186/s40001-024-02016-x
PMID:39152472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11330049/
Abstract

BACKGROUND

Salidroside (SAL), derived from Rhodiola, shows protective effects in pulmonary arterial hypertension (PAH) models, but its mechanisms are not fully elucidated.

OBJECTIVES

Investigate the therapeutic effects and the mechanism of SAL on PAH.

METHODS

Monocrotaline was used to establish a PAH rat model. SAL's impact on oxidative stress and inflammatory responses in lung tissues was analyzed using immunohistochemistry, ELISA, and Western blot. Untargeted metabolomics explored SAL's metabolic regulatory mechanisms.

RESULTS

SAL significantly reduced mean pulmonary artery pressure, right ventricular hypertrophy, collagen deposition, and fibrosis in the PAH rats. It enhanced antioxidant enzyme levels, reduced inflammatory cytokines, and improved NO bioavailability by upregulating endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) and decreases the expression of endothelin-1 (ET-1). Metabolomics indicated SAL restored metabolic balance in PAH rats, particularly in arginine metabolism.

CONCLUSIONS

SAL alleviates PAH by modulating arginine metabolism, enhancing NO synthesis, and improving pulmonary vascular remodeling.

摘要

背景

红景天苷(SAL)来源于红景天,在肺动脉高压(PAH)模型中显示出保护作用,但作用机制尚未完全阐明。

目的

研究 SAL 对 PAH 的治疗作用及机制。

方法

应用野百合碱建立 PAH 大鼠模型。采用免疫组织化学、ELISA 和 Western blot 分析 SAL 对肺组织氧化应激和炎症反应的影响。非靶向代谢组学探索 SAL 的代谢调节机制。

结果

SAL 可显著降低 PAH 大鼠的平均肺动脉压、右心室肥厚、胶原沉积和纤维化。它通过上调内皮型一氧化氮合酶(eNOS)、可溶性鸟苷酸环化酶(sGC)、环磷酸鸟苷(cGMP)和蛋白激酶 G(PKG),增加抗氧化酶水平,减少炎症细胞因子,提高一氧化氮(NO)的生物利用度,同时降低内皮素-1(ET-1)的表达,从而改善 NO 生物利用度。代谢组学表明,SAL 可恢复 PAH 大鼠的代谢平衡,尤其是精氨酸代谢。

结论

SAL 通过调节精氨酸代谢、增强 NO 合成和改善肺血管重塑来缓解 PAH。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/8e1ecf8ec82b/40001_2024_2016_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/5db913bf12a8/40001_2024_2016_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/fd42933d4bb4/40001_2024_2016_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/ac0ca6de89bd/40001_2024_2016_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/6326022d0f33/40001_2024_2016_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/d3f9396debde/40001_2024_2016_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/8e1ecf8ec82b/40001_2024_2016_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/5db913bf12a8/40001_2024_2016_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/fd42933d4bb4/40001_2024_2016_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/ac0ca6de89bd/40001_2024_2016_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/6326022d0f33/40001_2024_2016_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/d3f9396debde/40001_2024_2016_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a6/11330049/8e1ecf8ec82b/40001_2024_2016_Fig6_HTML.jpg

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