Ginsenoside Rg1 ameliorates hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and inflammation by regulating CCN1
Ginsenoside Rg1 ameliorates hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and inflammation by regulating CCN1
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DOI：
10.1016/j.biopha.2023.114920
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发表时间：
2023-05-20
影响因子：
7.5
通讯作者：
Wang，Hong-xin
中科院分区：
文献类型：
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作者：
Tang，Bai-lin;Liu，Yu;Wang，Hong-xin
肺动脉高压(PAH)是一种以血管重构为特征的慢性阻塞性疾病。已有研究证实人参皂苷Rg1能在一定程度上改善低氧性肺动脉高压，但其改善缺氧性肺动脉高压的可能机制尚不清楚。本研究旨在探讨人参皂苷Rg1对缺氧性肺高压的治疗作用。结果表明，低氧可促进炎症、内源性MT和血管重塑，并伴有CCN1水平下降和p-NFκBp65、β-1和p-Smad2/3水平升高。人参皂苷Rg1、重组CCN1、BAY-11-7082和SB-431542可抑制低氧诱导的血管重塑，减少低氧诱导的炎症细胞因子肿瘤坏死因子-α和白介素1β的表达，抑制间充质标志物α-SMA和Vimentin的表达，恢复内皮细胞标志物CD31和VE-钙粘素的表达，从而改善低氧诱导的内皮细胞内膜损伤，其机制可能与上调CCN1蛋白表达，下调p-NFκBp65、β-1和p-Smad2/3的表达有关。SiRNACCN1可上调p-NFκB p65、β-1和p-Smad2/3的表达，加速缺氧后炎症和内源性MT的发生和发展。综上所述，我们的研究表明，低氧诱导的EndMT和炎症在缺氧性肺动脉高压(HPH)中起一定作用。人参皂苷Rg1可通过调节CCN1逆转缺氧诱导的EndMT和炎症反应，对HPH具有潜在的防治价值。
Pulmonary arterial hypertension (PAH) is a chronic obstructive disease characterized by vascular remodeling. Studies have confirmed that ginsenoside Rg1 can improve pulmonary hypertension to a certain extent, but the potential mechanism by which it improves hypoxia-induced PAH remains unclear. The aim of this study was to investigate the therapeutic effect of ginsenoside Rg1 on hypoxia-induced PAH. The results showed that hypoxia promoted inflammation, EndMT, and vascular remodeling, which were accompanied by decreased CCN1 levels and increased p-NFκB p65, TGF-β1, and p-Smad 2/3 levels. Treatment with ginsenoside Rg1, recombinant CCN1, BAY-11-7082, and SB-431542 could prevent hypoxia-induced vascular remodeling, reduce the expression of the hypoxia-induced inflammatory cytokines TNF-α and IL-1β, inhibit the expression of the mesenchymal markers α-SMA and Vimentin and restore the expression of the endothelial markers CD31 and VE-cadherin to improve hypoxia-induced EndMT, which may be associated with the upregulation of CCN1 protein expression and downregulation of p-NFκB p65, TGF-β1, and p-Smad 2/3 in rats and cells. siRNA CCN1 transfection increased the expression of p-NFκB p65, TGF-β1, and p-Smad 2/3 and accelerated the occurrence and development of inflammation and EndMT after hypoxia. In summary, our study indicated that hypoxia-induced EndMT and inflammation play a role in hypoxic pulmonary hypertension (HPH). Ginsenoside Rg1 treatment could reverse hypoxia-induced EndMT and inflammation by regulating CCN1 and has potential value in the prevention and treatment of HPH.