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Archive > Volume 17 Issue 2 > 2025,17(2):340-351. DOI:https://doi.org/10.1016/j.chmed.2024.11.004 Prev Next

通過(guò)具有線粒體靶向作用的八聚精氨酸修飾的艷山姜揮發(fā)油脂微球緩解脂多糖誘導(dǎo)的血管內(nèi)皮炎癥損傷

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Ameliorating vascular endothelial injury for lipolysacharide-induced via mitochondrial targeting function of octaarginine-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres

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    摘要:
    目的：探究經(jīng)八聚精氨酸（R8）修飾后的艷山姜揮發(fā)油（EOFAZ）脂微球（LM）用于心血管疾病治療的潛力。方法：通過(guò)將EOFAZ本身的揮發(fā)油特征與LM的油相結(jié)合，并利用LM具有的血管內(nèi)皮損傷部位靶向優(yōu)勢(shì)，表面修飾細(xì)胞穿膜肽R8，制備了八聚精氨酸（Octaarginine , R8）修飾的艷山姜揮發(fā)油脂微球（EOFAZ@R8LM）。通過(guò)檢測(cè)線粒體膜電位（MMP）、細(xì)胞內(nèi)活性氧（ROS）水平和炎性因子白介素-6（IL-6）和白介素-1β（IL-1β）水平來(lái)評(píng)估該制劑緩解脂多糖（LPS）誘導(dǎo)的血管內(nèi)皮炎癥損傷能力。結(jié)果：EOFAZ@R8LM成功地將EOFAZ遞送至血管炎癥損傷部位并靶向血管內(nèi)皮細(xì)胞中的線粒體，通過(guò)調(diào)節(jié)線粒體膜電位和降低細(xì)胞內(nèi)ROS水平改善了線粒體功能障礙。此外，它還降低了炎癥因子IL-6和IL-1β的表達(dá)水平，從而發(fā)揮血管內(nèi)皮保護(hù)作用。結(jié)論：EOFAZ@R8LM在心血管治療方面具有巨大潛力，本文為開發(fā)有效治療心血管疾病的EOFAZ的臨床應(yīng)用新劑型提供了一種參考策略。

    Abstract:
    Objective: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@R8LM) for cardiovascular therapy. Methods: EOFAZ@R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1b (IL-1b) levels. Results: EOFAZ@R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1b, exerting protective effects on the vascular endothelium. Conclusion: Our findings highlight the significant therapeutic potential of EOFAZ@R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

    關(guān)鍵詞:
    艷山姜揮發(fā)油;炎癥;脂微球;線粒體功能障礙;八聚精氨酸;血管內(nèi)皮損傷

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    Project Supported:
    This work was supported by the National Natural Science Foundation of China (Nos. 82260827 and U1812403-4-4), the Guizhou Provincial Science Technology Project (No. ZK [2022]380), the Guizhou Provincial Natural Science Foundation (Nos. [2020] 1Z069 and [2020]1Y210), the Guizhou Provincial Scientific and Technologic Innovation Base (No. [2023]003) and the Cultivation Project of National Natural Science Foundation of Guizhou Medical University (Nos. 21NSFCP47 and 20NSP053), the High level Innovation Talents (No. GCC[2023]048).

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