蒙药蓝刺头对血管内皮细胞增殖和血管生成能力的潜在作用机制  

Mechanism of Mongolian medicine Echinops sphaerocephalus L.in proliferation and angiogenesis of vascular endothelial cells

作　　者：方源 钱智勇 何源哈达 王海燕 沙丽蓉 李筱贺 刘婧[4] 贺雅超 张凯 特木日巴根 Fang Yuan;Qian Zhiyong;He Yuanhada;Wang Haiyan;Sha Lirong;Li Xiaohe;Liu Jing;He Yachao;Zhang Kai;Temribagen(Graduate School,Inner Mongolia Medical University,Hohhot 010000,Inner Mongolia Autonomous Region,China;Bayannur Hospital,Bayannur 015000,Inner Mongolia Autonomous Region,China;Department of Human Anatomy,School of Basic Medicine,Inner Mongolia Medical University,Hohhot 010000,Inner Mongolia Autonomous Region,China;Bayannur Clinical College of Medicine,Inner Mongolia Medical University,Hohhot 010000,Inner Mongolia Autonomous Region,China;Department of Orthopedics,The Second Hospital of Ulanqab,Ulanqab 012000,Inner Mongolia Autonomous Region,China;Department of Orthopedics and Traumatology,Hohhot TCM Mongolian Hospital,Hohhot 010000,Inner Mongolia Autonomous Region,China)

机构地区：[1]内蒙古医科大学研究生院,内蒙古自治区呼和浩特市010000 [2]内蒙古巴彦淖尔市医院,内蒙古自治区巴彦淖尔市015000 [3]内蒙古医科大学基础医学院人体解剖教研室,内蒙古自治区呼和浩特市010000 [4]内蒙古医科大学巴彦淖尔临床医学院,内蒙古自治区呼和浩特市010000 [5]乌兰察布市第二医院骨科,内蒙古自治区乌兰察布市012000 [6]呼和浩特市中医蒙医医院蒙医骨伤科,内蒙古自治区呼和浩特市010000

出　　处：《中国组织工程研究》2025年第35期7519-7528,共10页Chinese Journal of Tissue Engineering Research

基　　金：内蒙古自治区卫生健康科技项目(202201188),项目负责人:王海燕;内蒙古自治区高等学校创新团队发展计划项目(NMGIRT2419),项目负责人:王海燕;内蒙古自治区高等学校创新团队发展计划项目(NMGIRT2227),项目负责人:李筱贺;2021年内蒙古自治区蒙医药协同创新中心科学研究项目(MYYXTYB202104),项目负责人:李筱贺;内蒙古医科大学2021年度校级科研重点项目(YKD2021ZD001),项目负责人:李筱贺;2021年乌兰察布市科技基础研究项目(2021JC321),项目负责人:张凯;内蒙古自然科学基金项目(2022MS08051),项目负责人:特木日巴根。

摘　　要：背景:蒙药蓝刺头对于筋伤骨折、骨不愈合、骨热、刺痛症、疮疡等疾病的疗效显著,是蒙医常用骨伤用药。课题组前期研究证实蒙药蓝刺头可促进骨髓间充质干细胞的增殖及成骨分化,但它对骨缺损修复过程中血管生成的影响尚未可知。目的:利用人脐静脉血管内皮细胞进行体外细胞实验,探讨蓝刺头对血管生成的影响,利用网络药理学技术挖掘蓝刺头中可能存在的促进血管形成的活性成分及其潜在作用机制。方法:制备蓝刺头乙醇提取物并冻干保存。观察不同质量浓度(1000,100,10μg/mL)蓝刺头干预对人脐静脉内皮细胞增殖、迁移、趋化及血管生成能力的影响。利用网络药理学对蒙药蓝刺头中具有促血管生成作用的有效成分及可能信号通路进行富集和分析。结果与结论:①蓝刺头对血管生成的影响受其质量浓度的调节:在低质量浓度(10μg/mL)条件下,蓝刺头能够促进人脐静脉血管内皮细胞的增殖、迁移、趋化及血管生成;相反,在高质量浓度(1000μg/mL)下,蓝刺头抑制人脐静脉内皮细胞的增殖、迁移和趋化,由于实验时间的限制,高质量浓度蓝刺头对血管生成的抑制作用并不显著。10μg/mL蓝刺头能够上调与血管生成相关因子(激酶插入域蛋白受体、血管内皮生长因A和缺氧诱导因子α)mRNA的表达,从而影响骨修复过程中的血管生成。②网络药理学分析表明,蓝刺头可能通过4种核心活性成分(芹菜素、咖啡酸、槲皮素和绿原酸)与8个核心靶点(TGFB1、TNF、IL-6、STAT3、CTNNB1、IL-1B、AKT1、HIF-1A)的结合,对血管生成、动脉粥样硬化、多种病毒感染以及肿瘤血管生成相关的信号通路产生影响。BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1000,100,and 10μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1000μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endot

关 键 词：蓝刺头 人脐静脉血管内皮细胞 血管生成 细胞增殖 网络药理学 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R313[医药卫生—临床医学] R285.5