Han Jin-Yi, Utsumi Hideo, Chung Han-Young
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, 1035 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Republic of Korea.
Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Antioxidants (Basel). 2025 Apr 20;14(4):497. doi: 10.3390/antiox14040497.
Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating the protective effects of antioxidants. In vitro, collagen induced dose-dependent platelet aggregation and increased ROS generation, evidenced by the enhanced EMPO adduct formation detected via electron spin resonance (ESR). In vivo experiments demonstrated that collagen administration significantly accelerated CAT-1 decay, indicating elevated oxidative stress with a transient peak around 1 minute post-treatment. Furthermore, escalating collagen doses correlated with increased ROS generation and reduced survival rates in mice, underscoring collagen's impact on oxidative stress and thrombosis severity. Importantly, treatment with enzymatic antioxidants (superoxide dismutase, catalase) and non-enzymatic antioxidants (DMTU, Tiron, mannitol) significantly attenuated collagen-induced oxidative stress and improved animal survival. Collectively, these findings elucidate the pivotal role of ROS in collagen-induced platelet activation and thrombosis and highlight antioxidants as promising therapeutic candidates for preventing thrombotic disorders and managing cardiovascular risk.
胶原蛋白在血小板活化和血栓形成中起着关键作用，然而，涉及活性氧（ROS）的潜在机制仍未完全明确。本研究调查了胶原蛋白在体外和体内如何调节ROS生成及血小板聚集，并评估了抗氧化剂的保护作用。在体外，胶原蛋白诱导剂量依赖性血小板聚集并增加ROS生成，通过电子自旋共振（ESR）检测到的增强的EMPO加合物形成证明了这一点。体内实验表明，给予胶原蛋白显著加速了CAT-1降解，表明氧化应激升高，在治疗后约1分钟出现短暂峰值。此外，胶原蛋白剂量增加与小鼠ROS生成增加和存活率降低相关，强调了胶原蛋白对氧化应激和血栓形成严重程度的影响。重要的是，用酶促抗氧化剂（超氧化物歧化酶、过氧化氢酶）和非酶促抗氧化剂（DMTU、Tiron、甘露醇）治疗可显著减轻胶原蛋白诱导的氧化应激并提高动物存活率。总的来说，这些发现阐明了ROS在胶原蛋白诱导的血小板活化和血栓形成中的关键作用，并突出了抗氧化剂作为预防血栓性疾病和管理心血管风险的有前景的治疗候选物。
