Liang Pan, Bi Tao, Zhou Yanan, Wang Chengmei, Ma Yining, Xu Houping, Shen Hongping, Ren Wei, Yang Sijin
National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
State Key Laboratories for Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China.
Small. 2023 Dec;19(49):e2303498. doi: 10.1002/smll.202303498. Epub 2023 Aug 22.
Achieving rapid and effective hemostasis remains a multidisciplinary challenge. Here, distinctive functional carbon dots derived from carbonized Platycladus orientalis (CPO-CDs) are developed using one-step hydrothermal method. The negatively charged surface of CPO-CDs retains partial functional groups from CPO precursor, exhibiting excellent water solubility and high biocompatibility. Both rat liver injury model and tail amputation model have confirmed the rapid and effective hemostatic performance of CPO-CDs on exogenous hemorrhage. Further, on endogenous blood-heat hemorrhage syndrome rat model, CPO-CDs could inhibit hemorrhage and alleviate inflammation response. Interestingly, the excellent hemostasis performance of CPO-CDs is ascribed to activate exogenous coagulation pathway and common coagulation pathway. More importantly, metabolomics of rat plasma suggests that the hemostasis effect of CPO-CDs is closely related to platelet functions. Therefore, the designed in vitro experiments are performed and it is discovered that CPO-CDs significantly promote platelets adhesion, activation, and aggregation. Further, the underlying mechanism investigation suggests that Src/Syk signal pathway plays a key role in platelets activation triggered by CPO-CDs. Overall, CPO-CDs with rapid and excellent hemostatic performance are discovered for the first time, which could be an excellent candidate for the treatment of hemorrhagic diseases.
实现快速有效的止血仍然是一个多学科面临的挑战。在此,采用一步水热法制备了源自碳化侧柏(CPO-CDs)的独特功能化碳点。CPO-CDs带负电荷的表面保留了来自CPO前体的部分官能团,表现出优异的水溶性和高生物相容性。大鼠肝损伤模型和断尾模型均证实了CPO-CDs对外源性出血具有快速有效的止血性能。此外,在内源性血热出血证大鼠模型上,CPO-CDs可抑制出血并减轻炎症反应。有趣的是,CPO-CDs优异的止血性能归因于激活外源性凝血途径和共同凝血途径。更重要的是,大鼠血浆代谢组学表明CPO-CDs的止血作用与血小板功能密切相关。因此,进行了体外实验,发现CPO-CDs显著促进血小板黏附、激活和聚集。进一步的潜在机制研究表明,Src/Syk信号通路在CPO-CDs触发的血小板激活中起关键作用。总体而言,首次发现了具有快速优异止血性能的CPO-CDs,其可能是治疗出血性疾病的优秀候选物。
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