Ginsenoside Rg1 ameliorates chronic intermittent hypoxia-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.
Ginsenoside Rg1 ameliorates chronic intermittent hypoxia-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.
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DOI：
10.1016/j.jgr.2022.07.006
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发表时间：
2023-01
影响因子：
6.3
通讯作者：
Hongxin Wang
中科院分区：
文献类型：
--
作者：
Fang Zhao;Meili Lu;Hongxin Wang
慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停（OSA）的主要病理生理特征，是导致心血管并发症的重要因素。钙蛋白酶-1的激活介导了内皮细胞活性氧（ROS）的产生，并损害了一氧化氮（NO）的生物利用度，导致血管内皮功能障碍（VED）。人参皂苷Rg 1被认为具有抗内皮细胞功能障碍的作用，但CIH诱导VED的可能机制尚不清楚。C57 BL/6小鼠和人冠状动脉内皮细胞（HCAECs）暴露于CIH敲除或过表达钙蛋白酶-1。在体内外实验中检测了Rg 1对VED、氧化应激、线粒体功能障碍以及calpain-1、PP 2A和p-eNOS表达水平的影响。CIH促进VED，氧化应激和线粒体功能障碍，伴随着钙蛋白酶-1和PP 2A水平的提高和p-eNOS水平的降低。人参皂苷Rg 1、calpain-1敲除、OKA、NAC和TEMPOL治疗可保护CIH诱导的VED、氧化应激和线粒体功能障碍，这可能与小鼠和细胞水平calpain-1和PP 2A蛋白表达下调以及p-eNOS上调有关。Calpain-1过表达增加了PP 2A的表达，降低了p-eNOS的水平，加速了CIH暴露后HCAECs VED、氧化应激和线粒体功能障碍的发生和发展。此外，O2·−、H2 O2、复合物Ⅰ或mitoKATP的清除剂可消除CIH诱导的内皮依赖性舒张功能损害。人参皂苷Rg 1可能通过抑制钙蛋白酶-1途径引起的线粒体活性氧的形成来减轻CIH诱导的血管内皮功能障碍。
As the major pathophysiological feature of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) is vital for the occurrence of cardiovascular complications. The activation of calpain-1 mediates the production of endothelial reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, resulting in vascular endothelial dysfunction (VED). Ginsenoside Rg1 is thought to against endothelial cell dysfunction, but the potential mechanism of CIH-induced VED remains unclear. C57BL/6 mice and human coronary artery endothelial cells (HCAECs) were exposed to CIH following knockout or overexpression of calpain-1. The effect of ginsenoside Rg1 on VED, oxidative stress, mitochondrial dysfunction, and the expression levels of calpain-1, PP2A and p-eNOS were detected both in vivo and in vitro. CIH promoted VED, oxidative stress and mitochondrial dysfunction accompanied by enhanced levels of calpain-1 and PP2A and reduced levels of p-eNOS in mice and cellular levels. Ginsenoside Rg1, calpain-1 knockout, OKA, NAC and TEMPOL treatment protected against CIH-induced VED, oxidative stress and mitochondrial dysfunction, which is likely concomitant with the downregulated protein expression of calpain-1 and PP2A and the upregulation of p-eNOS in mice and cellular levels. Calpain-1 overexpression increased the expression of PP2A, reduced the level of p-eNOS, and accelerated the occurrence and development of VED, oxidative stress and mitochondrial dysfunction in HCAECs exposed to CIH. Moreover, scavengers of O2•−, H2O2, complex Ⅰ or mitoKATP abolished CIH-induced impairment in endothelial-dependent relaxation. Ginsenoside Rg1 may alleviate CIH-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.
中药单体对离体缺氧大鼠脑线粒体氧化磷酸化和膜电位的影响
影响因子：
6.1
作者：
Yan W;Liu J
通讯作者：
Liu J