基于网络药理学研究丹参-川芎抗脑缺血再灌注损伤作用机制及试验验证

doi:10.16431/j.cnki.1671-7236.2022.09.038

摘要/Abstract

摘要： 【目的】通过网络药理学研究丹参-川芎药对治疗缺血性脑卒中的有效性成分及相应基因靶标，探讨其作用机制。【方法】应用中药系统药理学计数平台（TCMSP）、GeneCards、OMIM数据库，筛选出丹参-川芎药对治疗缺血性脑卒中的潜在靶点并进行GO功能和KEGG通路富集分析。分别设置假手术组、模型组、丹参-川芎低、中、高剂量组，采用预防和治疗给药方式对线栓制备的脑缺血再灌注模型大鼠进行干预，采用Zea-longa评分法对脑缺血再灌注24 h模型大鼠进行神经功能评分，苏木素-伊红（HE）染色法观察脑组织病理学变化进行初步验证。【结果】本研究共筛选到丹参-川芎药对主要有效活性成分共72个，其中川芎7个，丹参65个，缺血性脑卒中的靶点基因1 972个，有效活性成分与缺血性脑卒中共同作用靶标94个，包括IL6、IL10、TNF、MMP9、VEGFA、CASP3等；GO功能和KEGG通路富集结果提示，丹参-川芎药对治疗缺血性脑卒中与PI3K-Akt、cGMP-PKG、VEGF等多个信号通路有关。动物试验结果表明，丹参-川芎可减轻脑组织病理改变，减轻神经功能缺损，改善脑缺血再灌注损伤。【结论】丹参-川芎药对可能是通过PI3K/Akt信号通路改善脑缺血再灌注损伤，发挥抗细胞凋亡的作用。

关键词: 丹参-川芎; 脑缺血再灌注; 网络药理学; 药理作用机制

Abstract: 【Objective】 The experiment was aimed to study the effective components and corresponding gene targets of Salvia miltiorrhiza and Ligusticum chuanxiong in the treatment of ischemic stroke through network pharmacology, and to explore its mechanism of action.【Method】 Using Traditional Chinese Medicine System Pharmacology Enumeration Platform (TCMSP), GeneCards and OMIM database, the potential targets of Salvia miltiorrhiza and Ligusticum chuanxiong for the treatment of ischemic stroke were screened, and GO function and KEGG pathway enrichment analysis were carried out.The sham-operated group, the model group, and the low-dose, medium-dose and high-dose Salvia miltiorrhiza-Ligusticum chuanxiong groups were set up respectively, and the cerebral ischemia-reperfusion model rats prepared by suture were intervened by means of preventive and therapeutic administration.The 24-h blood reperfusion model rats were scored for neurological function by Zea-longa method, and hematoxylin-eosin (HE) staining was used to observe the pathological changes of brain tissue for preliminary verification.【Result】 In this study, a total of 72 main active ingredients of Salvia miltiorrhiza-Ligusticum chuanxiong pairs were screened, 7 from Ligusticum chuanxiong, 65 from Salvia miltiorrhiza, and 1 972 target genes for ischemic stroke.There were 94 common targets, including IL6, IL10, TNF, MMP9, VEGFA, CASP3, etc.The results of GO function and KEGG pathway enrichment suggested that the treatment of ischemic stroke by Salvia miltiorrhiza-Ligusticum chuanxiong was related to PI3K-Akt, cGMP-PKG, VEGF and other signal pathways.Animal experiments showed that Salvia miltiorrhiza-Ligusticum chuanxiong could reduce the pathological changes of brain tissue, reduce neurological deficits, and improve cerebral ischemia-reperfusion injury.【Conclusion】 Salvia miltiorrhiza-Ligusticum chuanxiong medicine pair might improve cerebral ischemia-reperfusion injury through PI3K/Akt signaling pathway, and played an anti-apoptotic effect.

Key words: Salvia miltiorrhiza-Ligusticum chuanxiong; cerebral ischemia-reperfusion; network pharmacology; pharmacological mechanism of action

中图分类号:

S853.74

付雪琴, 兰瑞, 邹旭欢, 王玮玮, 王漫漫. 基于网络药理学研究丹参-川芎抗脑缺血再灌注损伤作用机制及试验验证[J]. 中国畜牧兽医, 2022, 49(9): 3643-3654.

FU Xueqin, LAN Rui, ZOU Xuhuan, WANG Weiwei, WANG Manman. Action Mechanism of Salvia miltiorrhiza-Ligusticum chuanxiong Against Cerebral Ischemia-reperfusion Injury Based on Network Pharmacology and Experimental Verification[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(9): 3643-3654.

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