整合药理学方法的心可舒片干预动脉粥样硬化作用网络机制探讨  

An integrative pharmacological-based study on network mechanism of Xinkeshu Tablets intervention in atherosclerosis

作　　者：李晓宇[1,2,4] 徐男[1] 黄娜娜[3] 吴成胜 刘闰平 郭文鹤 李晓骄阳 孙蓉 LI Xiao-yu;XU Nan;HUANG Na-na;WU Cheng-sheng;LIU Run-ping;GUO Wen-he;LI Xiao-jiaoyang;SUN Rong(Shandong Academy of Chinese Medicine,Jinan 250014,China;Shandong University,Jinan 250100,China;The Second Hospital of Shandong University,Jinan 250033,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Department of Microbiology and Immunology,Virginia Commonwealth University,Richmond VA 23298,USA;Harbin University of Commerce,Harbin 150076,China;Affiliated Hospital of Taishan Medical University,Taian 271000,China)

机构地区：[1]山东省中医药研究院,山东济南250014 [2]山东大学,山东济南250100 [3]山东大学第二医院,山东济南250033 [4]山东中医药大学,山东济南250355 [5]弗吉尼亚联邦大学微生物学与免疫学系,美国弗吉尼亚州里士满23298 [6]哈尔滨商业大学,黑龙江哈尔滨150076 [7]泰山医学院附属医院,山东泰安271000

出　　处：《中草药》2018年第15期3463-3470,共8页Chinese Traditional and Herbal Drugs

基　　金：山东省重大产业专项：国家基药大品种心可舒片二次深度开发(2015ZDZX07002); 国家重大新药创制重大专项课题：中药复方药理学研究与药效评价关键技术(2009ZX09502-015); 山东省自主创新和成果转化课题：药物安全性评价和适宜于抗肿瘤及缺血性脑血管疾病多靶点和复方新药成药性评价关键技术研究(2014ZZCX02104); 泰山学者工程专项经费资助(Ns201511107)

摘　　要：目的探究心可舒片干预动脉粥样硬化(AS)作用的分子机制,对于心可舒片二次开发和临床应用提供参考。方法用整合药理学平台对心可舒片干预AS的关键靶点和通路进行预测,探究其干预AS的分子机制。结果通过建立心可舒片"中药-成分-靶点-通路"网络进行预测和分析,得到相关有效成分80个,确定了B4GALT4、B4GALT2、PRKCD、GCK、GNB1等关键靶点,明确了内分泌系统、甲状腺激素、神经系统、雌性激素和趋化因子等富集通路与其抗AS作用相关。结论心可舒片通过对PI3K/Akt/eNOS和Raf/MEK/ERK途径的共同调节,保护血管内皮细胞,从而达到干预AS的效果。Objective To explore the mechanism of the intervention of Xinkeshu Tablets（XKST） on atherosclerosis（AS） and provide reference for the secondary development and clinical application of XKST. Methods The integrated pharmacology platform was used to predict the key targets and pathways of the intervention of XKST on AS and its molecular mechanism was also explored. Results In the integrative analysis of heterogeneous network of ＂TCM-component-target-pathway＂, 80 relevant effective ingredients were found, including B4 GALT4, B4 GALT2, PRKCD, GCK, GNB1, and other key targets; Endocrine system, thyroid hormone signaling pathway, nervous system, estrogen signaling pathway, and chemokine signaling pathway were key pathways related with its anti-atherosclerosis. Conclusion According to the analysis and prediction of the enrichment information, the effect of XKST on common regulating PI3 K/Akt/e NOS and Raf/MEK/ERK signaling pathway and protecting vascular endothelial cells is first prompted, thus achieving the intervention in AS.

关 键 词：心可舒片 动脉粥样硬化 整合药理学平台 分子机制 PI3K/Akt/eNOS通路 Raf/MEK/ERK通路 

分 类 号：R285.5[医药卫生—中药学]