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赵冯岩,杨浩澜,朱炎贞,林美妤,刘芳.基于网络药理学从铁死亡途径研究补阳还五汤调控缺血性脑卒中的作用机制[J].湖南中医药大学学报英文版,2021,41(7):1065-1072.[Click to copy
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| 基于网络药理学从铁死亡途径研究补阳还五汤调控缺血性脑卒中的作用机制 |
| 赵冯岩,杨浩澜,朱炎贞,林美妤,刘芳 |
| (湖南中医药大学药学院, 湖南 长沙 410208;湖南省中药饮片标准化及功能工程技术研究中心, 湖南 长沙 410208;湖南中医药大学中西医结合学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 利用网络药理学方法探究补阳还五汤经由铁死亡途径调控缺血性脑卒中的作用机制。方法 通过TCMSP、PharmMapper数据库完成补阳还五汤处方中各药物的化学成分、靶点基因及其相应对接得分的收集，采用KEGG、GeneCards数据库获取疾病相关靶点；采用Cytoscape 3.6.1获取补阳还五汤调控缺血性脑卒中铁死亡途径的作用候选靶点网络图，并对该图进行模块分析和二次筛选；KOBAS 3.0对候选靶点与模块基因进行KEGG通路富集；采用Western blot技术检测PC12细胞氧化应激模型p-PI3K、PI3K、p-Akt、Akt、p-mTOR、mTOR蛋白表达。结果 共得到补阳还五汤主要活性成分10个，综合文献分析得缺血性脑卒中铁死亡途径关键靶点3个，主要KEGG通路7条。验证实验结果提示补阳还五汤通过PI3K-Akt-mTOR信号通路对氧化应激损伤的PC12细胞发挥保护作用。结论 补阳还五汤调控缺血性脑卒中铁死亡途径可能与HSP90AA1、EGFR、GRB2等靶点及MAPK、PI3K-Akt等信号通路有关，其中HSP90AA1靶点和PI3K-Akt信号通路可能是关键机制之一。 |
| 关键词: 铁死亡 补阳还五汤 缺血性脑卒中 网络药理学 |
| DOI：10.3969/j.issn.1674-070X.2021.07.016 |
| Received:March 23, 2021 |
| 基金项目:国家自然科学基金项目（81704064）；湖南省教育厅科学研究优秀青年项目（20B434）；湖南省中医药管理局科研项目（202177）；湖南中医药大学大学生创新创业计划项目（2020-112）；2018年湖南省青年教师培养对象资助项目；湖南省中药学一流学科资助项目（校行科字[2018]3号）。 |
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| Exploring the Mechanism of Buyang Huanwu Decoction Regulating on Cerebral Ischemic Stroke Through Ferroptosis Based on Network Pharmacology |
| ZHAO Fengyan,YANG Haolan,ZHU Yanzhen,LIN Meiyu,LIU Fang |
| (Pharmacy School, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, Hunan 410208, China;College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To use network pharmacology to explore the mechanism of Buyang Huanwu Decoction regulating ischemic stroke through ferroptosis. Methods The chemical components, target genes of Buyang Huanwu Decoction and their corresponding docking scores were collected by TCMSP database or PharmMapper database, and the disease-related targets were obtained through KEGG and GeneCards database; the Cytoscape 3.6.1 software was used to get the network map of candidate targets of Buyang Huanwu Decoction effect on cerebral ischemic stroke by ferroptosis pathway, and the network map of candidate targets was screened twice and MCODE analysis subsquently; the candidate targets and module genes were enriched by KEGG pathway in KOBAS 3.0. Western blot were used to detect the expression of p-PI3K, PI3K, p-Akt, Akt, p-mTOR and mTOR protein in PC12 cells model with oxidative stress injury. Results There were 10 potential active ingredients in Buyang Huanwu Decoction, and 3 key targets and 7 main KEGG pathways in cerebral ischemic stroke by ferroptosis based on the literature analysis. And the validation experiment confirmed that Buyang Huanwu Decoction can protect oxidative stress induced PC12 cells injure via PI3K-Akt-mTOR signal pathway. Conclusion Buyang Huanwu Decoction in regulating cerebral ischemic stroke by ferroptosis may be related to HSP90AA1, EGFR, GRB2 and other signal pathways such as MAPK and PI3K-Akt. Among which the HSP90AA1 and PI3K-Akt signaling pathway may be one of the most crucial mechanisms. |
| Key words: ferroptosis Buyang Huanwu Decoction cerebral ischemic stroke network pharmacology |
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