摘要
目的采用网络药理学探讨葛根-丹参药对治疗缺血性脑卒中(ischemic stroke,IS)的作用机制,并进行体内实验验证。方法采用大脑中动脉闭塞(MCAO)法复制IS大鼠模型,造模成功后分别用葛根、丹参、葛根-丹参药对低剂量和葛根-丹参药对高剂量干预7 d,TTC染色法测定大鼠脑梗死面积;通过TCMSP、GeneCards等数据库获得葛根-丹参作用于IS的靶点并进行GO功能富集分析和KEGG通路富集分析;Western blot对预测的通路进行初步验证。结果网络药理学预测分析显示,葛根-丹参药对的潜在活性成分有66个,作用于IS的关键成分为大豆苷元、木犀草素、葛根素、鼠尾草酚酮、β-谷甾醇、丹参酮IIA,关键靶点为白细胞介素(IL)-6、肿瘤蛋白p53(TP53)、血管内皮生长因子(VEGF)A、丝裂原活化蛋白激酶(MAPK)1、肿瘤坏死因子(TNF),可能的作用机制与磷脂酰肌醇-3-激酶-丝氨酸/苏氨酸-蛋白激酶B(PI3K-Akt)信号通路、缺氧诱导因子(HIF)-1信号通路、IL-17信号通路、TNF信号通路、VEGF信号通路等有关;动物实验验证结果表明,葛根-丹参干预后,MCAO大鼠的脑梗死面积明显缩小(P<0.01),大鼠脑组织中磷酸化(p)-PI3K/PI3K、p-Akt/Akt显著升高(P<0.05)。结论葛根-丹参药对可明显减小脑梗死面积、减轻脑损伤,该作用可能与调控PI3K-Akt信号通路有关。
Objective The mechanism of Gegen-Danshen drug pair in the treatment of ischemic stroke(IS)was investigated by network pharmacology and experimental verification in vivo.Methods IS rat models were established by MCAO method,and administered with Gege,Danshen,low dose of Gegen-Danshen drug pair and high dose of Gegen-Danshen drug pair for 1 week.The infarction area was measured by TTC staining.The potential targets of Gegen-Danshen drug pair in treating IS were obtained by TCMSP,GeneCards and other databases.GO functional enrichment analysis and KEGG pathway enrichment analysis were performed.The predicted pathway was preliminarily verified by Western blot.Results Through network pharmacological analysis,66 potential active components of Gegen-Danshen drug pair were obtained.The key components were daidzein,luteolin,puerarin,salviolone,beta-sitosterol and tanshinone IIA.The key targets were IL6,TP53,VEGFA,MAPK1 and TNF.The possible mechanism was related to PI3K-Akt signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,TNF signaling pathway,VEGF signaling pathway and other signaling pathways.The experimental results showed that after the intervention of Gegen-Danshen drug pair,the cerebral infarction area of MCAO rats was significantly reduced(P<0.01),and the expression of p-PI3K/PI3K and p-Akt/Akt in the brain tissue of MCAO rats was significantly increased(P<0.05).Conclusion Gegen-Danshen drug pair could significantly reduce the cerebral infarction area and alleviate the brain injury,which may be related to the regulation of PI3K-Akt signaling pathway.
作者
孙小鑫
王瑞海
苗青
刘丽梅
SUN Xiaoxin;WANG Ruihai;MIAO Qing;LIU Limei(Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Beijing Chunfeng Chinese Medicine Co.,Ltd.,Beijing 101400,China)
出处
《中国中医基础医学杂志》
2025年第2期272-279,共8页
JOURNAL OF BASIC CHINESE MEDICINE
基金
中央级公益性科研院所基本科研业务费专项(YZX-202209)。
