Wang Xiaobo, Fan Fuhan, Hou Ya, Meng Xianli
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.
Heliyon. 2024 Oct 4;10(20):e38958. doi: 10.1016/j.heliyon.2024.e38958. eCollection 2024 Oct 30.
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.
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。