PPARγ调控高血压的分子机制及中药干预的研究进展

    Research Progress on the Molecular Mechanism of PPARγ in Regulating Hypertension and the Intervention of Traditional Chinese Medicine

    • 摘要: 高血压是一种以血管功能障碍、氧化应激及炎症反应为核心的慢性疾病,涉及复杂的病理机制。PPARγ作为一种核转录因子,在血管稳态、炎症反应及肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)平衡调控中发挥着重要作用。本文系统阐述了PPARγ在高血压中的作用机制及中药通过调控PPARγ干预高血压的研究现状。研究表明,PPARγ的激活通过以下途径实现对高血压的多维度干预:抑制NF-κB等促炎信号通路并调节巨噬细胞极化以减轻炎症反应;通过抑制NADPH氧化酶活性、上调Nrf2抗氧化通路来缓解氧化应激;促进内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)活性增加NO生成、抑制内皮素-1(endothelin-1,ET-1)表达以改善血管内皮功能;此外,还可拮抗Ang Ⅱ 1型受体(angiotensin Ⅱ type 1 receptor,AT1R)并促进ACE2-Mas轴的表达以重塑RAAS平衡。 中药有效成分(如人参皂苷Rg1、鹰嘴豆芽素A、淫羊藿次苷Ⅱ、六氢姜黄素等)及复方(如芪黄逐瘀方、益气活血方、半夏白术天麻汤等)能够通过激活PPARγ及其共激活因子PGC-1α,抑制NF-κB信号通路,增强Nrf2抗氧化通路,并促进ACE2-Mas轴的表达,进而改善血管功能,减轻炎症反应和氧化应激,从而有效地防治高血压及其相关靶器官损伤。

       

      Abstract: Hypertension is a chronic disease characterized by vascular dysfunction, oxidative stress and inflammatory response, involving complex pathological mechanisms. PPARγ, as a nuclear transcription factor, plays a crucial role in the regulation of vascular homeostasis, inflammatory response and renin-angiotensin-aldosterone system(RAAS) balance. This article systematically expounds the mechanism of PPARγ in hypertension and the current research status of traditional Chinese medicine in the intervention of hypertension through the regulation of PPARγ. Studies have shown that the activation of PPARγ can achieve multi-dimensional intervention in hypertension through the following pathways: inhibiting pro-inflammatory signaling pathways such as NF-κB and regulating macrophage polarization to alleviate inflammatory response; relieving oxidative stress by inhibiting NADPH oxidase activity and up-regulating the Nrf2 antioxidant pathway; promoting iendothelial nitric oxide synthase(eNOS) activity to increase NO production and inhibiting endothelin-1(ET-1) expression to improve vascular endothelial function; in addition, it can antagonize angiotensin Ⅱ type 1 receptor(AT1R) and promote the expression of ACE2-Mas axis to restore RAAS balance. The active components of traditional Chinese medicine(such as ginsenoside Rg1, biochanin A, icariiside Ⅱ, hexahydrocurcumin, etc.) and compound prescriptions(such as Qihuang Zhuyu Formula, Yiqi Huoxue Formula, Banxia Baizhu decoction, etc.) can improve vascular function, reduce inflammatory response and oxidative stress, and effectively prevent and treat hypertension and its related target organ damage by activating PPARγ and its coactivator PGC-1α, inhibiting NF-κB signaling pathway, enhancing Nrf2 antioxidant pathway, and promoting the expression of ACE2-Mas axis.

       

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