基于脑缺血关键病理模块阐释注射用丹参多酚酸主成分在神经保护中的协同作用  

Synergistic neuroprotective effects of main components of salvianolic acids for injection based on key pathological modules of cerebral ischemia

作　　者：谭思宇 吴亚旭 燕子姝 鞠爱春 李德坤 庄朋伟[1,4] 张艳军 郭虹 TAN Si-yu;WU Ya-xu;YAN Zi-shu;JU Ai-chun;LI De-kun;ZHUANG Peng-wei;ZHANG Yan-jun;GUO Hong(Haihe Laboratory of Modern Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300193,China;Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300402,China)

机构地区：[1]天津中医药大学现代中医药海河实验室,天津301617 [2]天津中医药大学省部共建组分中药国家重点实验室,天津301617 [3]天津中医药大学第一附属医院,天津300193 [4]国家中医针灸临床医学研究中心,天津300193 [5]天津天士力之骄药业有限公司,天津300402

出　　处：《中国中药杂志》2025年第3期693-701,共9页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82174112);中医药重点领域科研课题(2024008)。

摘　　要：该研究旨在探讨注射用丹参多酚酸(SAFI)的主要成分在脑缺血关键病理环节中的协同作用,以明确其脑保护药效的特点。研究通过单细胞数据挖掘,识别出与脑缺血相关的内皮损伤和神经炎症2类主要病理基因模块,结合网络医学中的拓扑距离计算,筛选出SAFI主要成分间可能存在的协同作用药物组合。研究发现,咖啡酸与丹酚酸B的组合在应对内皮损伤和神经炎症方面综合评分最高,存在潜在协同作用。进一步的体外细胞实验验证结果显示这2种成分按1∶1组合给药时,能够显著保护脑微血管内皮细胞(bEnd.3)免受氧糖剥夺/复氧(OGD/R)诱导的再灌注损伤,并有效抑制脂多糖(LPS)诱导的小胶质细胞(BV-2)神经炎症反应。该研究为揭示中药活性成分间的协同作用提供了新的方法,并为深入理解中药多成分、多靶点的作用机制提供了新的研究思路。This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.

关 键 词：注射用丹参多酚酸 药物协同作用 缺血性卒中 内皮损伤 神经炎症 

分 类 号：R285[医药卫生—中药学]