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标题:构建用于清除小鼠低压低氧诱导脑损伤中活性氧的特异性纳米探针。

Tile: Construction of a specific nanoprobe for scavenging ROS in hypobaric hypoxia induced brain injury of mice.

作者信息

Wang Xiaobo, Fan Fuhan, Hou Ya, Meng Xianli

机构信息

Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

出版信息

Heliyon. 2024 Oct 4;10(20):e38958. doi: 10.1016/j.heliyon.2024.e38958. eCollection 2024 Oct 30.

DOI:10.1016/j.heliyon.2024.e38958
PMID:39640698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11620081/
Abstract

The prevention and treatment of hypobaric hypoxia brain injury (HHBI) remains an unprecedented challenge due to the complex oxidative stress response at the damage site. In this study, RuCO phthalocyanine compound (RuPc) and bovine serum albumin (BSA) were self-assembled to obtain RuPc-BSA nanoparticles for HHBI therapy. As a nanoprobe carrying and storing carbon monoxide (CO), RuPc-BSA delivers CO to pathologically damaged areas of the brain. CO specifically attaches itself to the heme functional groups on mitochondria and restricts the source of reactive oxygen species (ROS) generation. RuPc-BSA nanoparticles have been demonstrated to exhibit amazing stability as well as remarkable scavenging activity on hydroxyl radical, superoxide anion, and hydrogen peroxide. experiments showed that ROS levels in the brain of HHBI rats pretreated with RuPc-BSA decreased significantly, and neuronal function and oxidative stress levels were alleviated. Western blot and qRT-RCR results indicated that RuPc-BSA restricted the protein levels of Keap1, whereas enhanced the gene and protein levels of Nrf2. This study demonstrated that RuPc-BSA can ameliorate HHBI of mice by scavenging ROS partly via activating Keap1/Nrf2 signaling pathway.

摘要

由于损伤部位复杂的氧化应激反应,低压缺氧性脑损伤(HHBI)的防治仍然是一个前所未有的挑战。在本研究中,将钌酞菁化合物(RuPc)与牛血清白蛋白(BSA)自组装,以获得用于HHBI治疗的RuPc-BSA纳米颗粒。作为一种携带和储存一氧化碳(CO)的纳米探针,RuPc-BSA将CO输送到大脑的病理损伤区域。CO特异性地附着于线粒体上的血红素官能团,并限制活性氧(ROS)的产生来源。已证明RuPc-BSA纳米颗粒具有惊人的稳定性以及对羟基自由基、超氧阴离子和过氧化氢的显著清除活性。实验表明,用RuPc-BSA预处理的HHBI大鼠大脑中的ROS水平显著降低,神经元功能和氧化应激水平得到缓解。蛋白质免疫印迹和qRT-RCR结果表明,RuPc-BSA可降低Keap1的蛋白水平,同时提高Nrf2的基因和蛋白水平。本研究表明,RuPc-BSA可通过激活Keap1/Nrf2信号通路部分清除ROS,从而改善小鼠的HHBI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/aa070f6d2ca3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/fcc12dad9f23/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/ac4aaa5da686/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/9b3152e0ef2f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/7a0a60e19305/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/b6d8410f3e65/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/aa070f6d2ca3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/fcc12dad9f23/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/ac4aaa5da686/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/9b3152e0ef2f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/7a0a60e19305/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/b6d8410f3e65/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cc8/11620081/aa070f6d2ca3/gr6.jpg

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本文引用的文献

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Barrier Functional Integrity Recording on bEnd.3 Vascular Endothelial Cells via Transendothelial Electrical Resistance Detection.通过跨内皮电阻检测对 bEnd.3 血管内皮细胞进行屏障功能完整性记录。
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Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis.姜黄素通过 ROS/KEAP1/NRF2/miR-34a/b/c 级联反应抑制结直肠癌细胞转移。
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Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema.
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FUNDC1-mediated mitophagy and HIF1α activation drives pulmonary hypertension during hypoxia.FUNDC1 介导的线粒体自噬和 HIF1α 激活驱动低氧性肺动脉高压。
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NRF1-mediated microglial activation triggers high-altitude cerebral edema.NRF1 介导的小胶质细胞激活引发高原脑水肿。
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Rhodiola crenulate alleviates hypobaric hypoxia-induced brain injury via adjusting NF-κB/NLRP3-mediated inflammation.秀丽红景天通过调节 NF-κB/NLRP3 介导的炎症缓解低压缺氧诱导的脑损伤。
Phytomedicine. 2022 Aug;103:154240. doi: 10.1016/j.phymed.2022.154240. Epub 2022 Jun 3.
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Salidroside attenuates high altitude hypobaric hypoxia-induced brain injury in mice via inhibiting NF-κB/NLRP3 pathway.红景天苷通过抑制 NF-κB/NLRP3 通路减轻小鼠高原低压缺氧诱导的脑损伤。
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Salidroside, a phenyl ethanol glycoside from Rhodiola crenulata, orchestrates hypoxic mitochondrial dynamics homeostasis by stimulating Sirt1/p53/Drp1 signaling.红景天苷是一种来源于大花红景天的苯乙醇苷,它通过刺激Sirt1/p53/Drp1信号通路来协调缺氧状态下的线粒体动力学稳态。
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Dengzhan Xixin injection derived from a traditional Chinese herb Erigeron breviscapus ameliorates cerebral ischemia/reperfusion injury in rats via modulation of mitophagy and mitochondrial apoptosis.灯盏细辛注射液源于一种传统中药灯盏细辛,可通过调节细胞自噬和线粒体凋亡来改善大鼠脑缺血再灌注损伤。
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