Wang Jiahui, Cao Yang, Zhe Yadong, Taylor Marcus, Liu Zhigang, Zhao Chenyu
Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
J Thorac Dis. 2025 Jun 30;17(6):4145-4158. doi: 10.21037/jtd-2025-866. Epub 2025 Jun 26.
Neurological deficit is a common complication of deep hypothermic circulatory arrest (DHCA). Among the diverse factors contributing to neural injury, oxidative stress plays a prominent role. Emerging nanocluster technology has demonstrated considerable antioxidant and anti-inflammation activity. In this study, we developed a novel type of nanocluster for the treatment of neural injury induced by DHCA.
Single atom-substituted gold nanoclusters (AuNCs) were synthesized. PC-12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and a rat DHCA model were employed. Cell viability was evaluated via Cell Counting Kit-8 (CCK-8). Histopathological changes in the hippocampus were evaluated by hematoxylin-eosin staining. S100 calcium-binding protein β (S100β), neuron-specific enolase (NSE), malondialdehyde (MDA), and interleukin-1β (IL-1β) levels were determined by enzyme-linked immunosorbent assay (ELISA). Expression of S100β, caspase-3, and cleaved caspase-3 was assessed via Western blotting.
AuNCs exhibited strong antioxidant capacities, mimicking superoxide dismutase (SOD) and catalase (CAT) activities. studies demonstrated improved neuronal survival following OGD/R. , DHCA-induced hippocampal damage was significantly alleviated by AuNCs treatment, as evidenced by reduced histological neuronal degeneration, decreased levels of inflammatory cytokines (TNF-α and IL-1β), and downregulation of apoptotic markers (caspase-3 and cleaved caspase-3).
The newly developed AuNCs alleviated the neural injury induced by DHCA through anti-inflammation, antioxidant, and anti-apoptosis activity. These findings offer a novel avenue for achieving perioperative brain protection in clinical DHCA and provide a new direction for developing catalysts in medical applications.
神经功能缺损是深低温停循环（DHCA）的常见并发症。在导致神经损伤的多种因素中，氧化应激起着重要作用。新兴的纳米团簇技术已显示出可观的抗氧化和抗炎活性。在本研究中，我们开发了一种新型纳米团簇用于治疗DHCA诱导的神经损伤。
合成了单原子取代的金纳米团簇（AuNCs）。采用氧糖剥夺/复氧（OGD/R）处理的PC-12细胞和大鼠DHCA模型。通过细胞计数试剂盒-8（CCK-8）评估细胞活力。通过苏木精-伊红染色评估海马的组织病理学变化。通过酶联免疫吸附测定（ELISA）测定S100钙结合蛋白β（S100β）、神经元特异性烯醇化酶（NSE）、丙二醛（MDA）和白细胞介素-1β（IL-1β）水平。通过蛋白质印迹法评估S100β、半胱天冬酶-3和裂解的半胱天冬酶-3的表达。
AuNCs表现出强大的抗氧化能力，模拟超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。研究表明OGD/R后神经元存活率提高。此外，AuNCs治疗显著减轻了DHCA诱导的海马损伤，表现为组织学上神经元变性减少、炎性细胞因子（TNF-α和IL-1β）水平降低以及凋亡标志物（半胱天冬酶-3和裂解的半胱天冬酶-3）下调。
新开发的AuNCs通过抗炎、抗氧化和抗凋亡活性减轻了DHCA诱导的神经损伤。这些发现为临床DHCA围手术期脑保护提供了一条新途径，并为医学应用中开发催化剂提供了新方向。
