藤丹胶囊通过介导芳香烃受体信号通路对原发性高血压大鼠血管内皮功能的影响  

Effetcts of Tengdan Capsule on vascular endothelial function in essential hypertension rats by mediating aryl hydrocarbon receptor signaling pathway

作　　者：杜晓鹂 朱琳[1,2] 赵震邦 董玉 张家琪 常静 陶倩倩 范斯文 贺爽 朱彦[1,2] DU Xiao-li;ZHU Lin;ZHAO Zhen-bang;DONG Yu;ZHANG Jia-qi;CHANG Jing;TAO Qian-qian;FAN Si-wen;HE Shuang;ZHU Yan(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;National Key Laboratory of Component Traditional Chinese Medicine,Tianjin 301617,China;School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China)

机构地区：[1]天津中医药大学,天津301617 [2]组分中药国家重点实验室,天津301617 [3]内蒙古医科大学药学院,呼和浩特010110

出　　处：《中华中医药杂志》2021年第5期2664-2669,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81873037);内蒙古自然科学基金项目(No.2020MS08133);内蒙古自治区蒙药药效物质基础与质量控制工程技术研究中心项目。

摘　　要：目的:利用网络药理学构建藤丹胶囊治疗原发性高血压的"活性成分-通路-作用靶点"互作网络,并进行实验验证。方法:通过网络药理学预测藤丹胶囊治疗原发性高血压的活性成分、作用靶点,利用IPA生物信息学软件对潜在靶点进行核心分析;采用超声法制备藤丹胶囊的甲醇提取物,利用HPLC技术对其中主要活性成分进行验证;以离体原发性高血压大鼠主动脉环模型为基础,进一步探讨藤丹胶囊扩张血管的信号机制。结果:通过检索数据库与相关文献,筛选出118种较高活性化合物,可能作用于高血压病的潜在靶点有276个。IPA核心分析显示藤丹胶囊影响的前10条通路。槲皮素是藤丹胶囊中多种中草药中富集的活性成分之一,不仅能同时作用于多个靶点,还能通过作用于IL-6、NF-κB、NQO、CYP1A1、CYP1B1等主要靶点调控芳香烃受体信号通路。HPLC分析证实了藤丹胶囊中含有槲皮素和另外一种黄酮化合物木犀草素。体外主动脉环实验表明,与WKY组比较,模型组大鼠主动脉的内皮依赖型血管舒张功能显著受损(P<0.05),而TDC组可显著改善血管舒张功能(P<0.01)。结论:藤丹胶囊通过介导芳香烃受体信号通路保护原发性高血压大鼠内皮功能。Objective:The interaction network of’active ingredient,pathway and target’of Tengdan Capsule in the treatment of essential hypertension was established by network pharmacology,and the experimental verification was carried out.Methods:The active ingredients and targets of Tengdan Capsule in the treatment of essential hypertension were predicted by network pharmacology,and the potential targets were analyzed by IPA bioinformatics software.The methanol extract of Tengdan Capsule was prepared by ultrasonic method,and the main active components were verified by HPLC.Based on the aortic ring model of rats with essential hypertension in vitro,the signal mechanism of Tengdan Capsule was further investigated.Results:By searching the database and related literature,118 compounds with high activity were screened out,and 276 potential targets were identified.IPA core analysis showed the top 10 pathways affected by Tengdan Capsule.Quercetin was one of the active components enriched in various Chinese herbal medicines in Tentangdan Capsule.Quercetin could not only act on multiple targets simultaneously,but also regulate the aromatic hydrocarbon receptor signaling pathway by acting on IL-6,NF-κB,NQO,CYP1 A1,CYP1 B1 and other major targets.HPLC analysis confirmed the presence of quercetin and luteolin,another flavonoid compound in Tengdan Capsule.In vitro aortic ring experiments showed that endothelium-dependent vasodilation of the SHR aorta was significantly impaired in the model group compared with the WKY group(P<0.05),while Tengdan Capsule group could significantly improve vasodilator function(P<0.01).Conclusion:Tengdan Capsule protect endothelial function in essential hypertensive rats by mediating aromatic hydrocarbon receptor signaling pathway.

关 键 词：藤丹胶囊 芳香烃受体信号通路 槲皮素 内皮功能 原发性高血压 主动脉环 

分 类 号：R285[医药卫生—中药学]