Salidroside ameliorates hypoxic pulmonary hypertension by regulating the two-pore domain potassium TASK-1 channel.

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2024-10-30 DOI:10.1016/j.phymed.2024.156206

Zheng-Yu Sun, Guo-Qing Lu, Hong-Yan Sun, Wen-Di Jiang, Lei Wang, Yu-Hang Wang, Le-Qiang Liu, Hong-Ju Wang, Bi Tang, Qin Gao, Pin-Fang Kang

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Abstract

Background: Hypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo.

Methods: A rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays.

Results: Sal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, suppressed the proliferation, and enhanced the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel.

Conclusions: Sal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH.

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水杨甙通过调节双孔结构域钾 TASK-1 通道改善缺氧性肺动脉高压。

背景：缺氧性肺血管收缩（HPV）是血管平滑肌的反射性收缩。本研究旨在探讨Salidroside（Sal）在体外和体内肺动脉扩张中的作用以及Sal调节缺氧性肺动脉高压的潜在机制：方法：利用缺氧室构建大鼠缺氧性肺动脉高压（HPH）模型。方法：利用缺氧室构建大鼠缺氧性肺动脉高压（HPH）模型，采用血管环、全细胞膜片钳、WGA染色、HE染色和天狼星猩红染色等方法评估盐对HPH的影响：结果：盐治疗减轻了急性缺氧对SD大鼠肺循环的损伤。同时，盐治疗可降低急性缺氧对肺血管张力的影响，且呈浓度依赖性，这与TWIK相关酸敏钾通道1（TASK-1）介导的舒张效应有关。我们发现，盐处理能以浓度依赖性方式明显增加肺动脉平滑肌细胞（PASMCs）的 TASK-1 电流，并能逆转急性缺氧对 TASK-1 电流的抑制作用。此外，在持续缺氧条件下，Sal 还能提高 SD 大鼠肺动脉平滑肌细胞的 TASK-1 电流密度、抑制其增殖并促进其凋亡。此外，我们还发现，通过调节TASK-1通道，盐治疗可改善PASMCs的电生理重塑和肺血管重塑：结论：盐可以通过恢复TASK-1通道的功能来缓解HPH，为治疗HPH提供了一种新的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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上海源叶	Sal	≥98%

来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.