摘要
目的:在确定灯盏生脉胶囊抗慢性脑缺血作用基础上,采用网络药理学技术对其可能的作用机制进行解析。方法:采用右侧颈总动脉结扎法制备慢性脑缺血模型,分为假手术组、模型组、金纳多组(48 mg·kg^(-1))、灯盏生脉胶囊低、高剂量组(0.0405、0.162 g·kg^(-1))。通过Morris水迷宫实验及旷场实验对其药效进行评价,基于PubChem、GeneCards、Metascape等数据库进行靶点搜集、富集等分析,通过STRING 11.0、Cytoscape 3.7.1构建灯盏生脉胶囊成分靶点与慢性脑缺血疾病靶点相互作用网络、核心靶点网络及“成分-核心靶标-通路”网络,采用网络药理学对其作用机制进行探究,并通过分子生物学实验进行了验证。结果:训练第3~5天,灯盏生脉胶囊低剂量组小鼠的逃避潜伏期明显缩短;灯盏生脉胶囊高、低剂量组小鼠的穿越平台次数、原平台象限停留时间、总运动距离及中央区域运动距离增加。网络药理学结果表明,灯盏生脉胶囊可能通过参与炎症反应、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、细胞因子-细胞因子受体相互作用、肿瘤坏死因子(TNF)信号通路、血液循环、血管生成、细胞外基质等相关的生物学过程及通路,干预白细胞介素-6(IL-6)、TNF、胰岛素样生长因子1(IGF1)、血管内皮生长因子A(VEGFA)和表皮细胞生长因子(EGF)等靶点发挥抗慢性脑缺血的作用。分析生物学实验验证结果表明,灯盏生脉胶囊可降低小鼠脑组织中IL-6表达。结论:灯盏生脉胶囊具有明显抗慢性脑缺血作用,网络药理学揭示了灯盏生脉胶囊多成分、多途径、多靶点的作用机制,为进一步深入研究其作用机制奠定了基础。
Objective:Based on the protective effect of Dengzhan Shengmai capsules(DZSM)on chronic cerebral hypoperfusion(CCH),network pharmacology was employed to investigate the molecular mechanism.Method:CCH model was established by right common carotid artery ligation.The mice were divided into sham operation group,model group,ginaton group(48 mg·kg^(-1)),DZSM low-and high-dose groups(0.0405,0.162 g·kg^(-1)).The efficacy was evaluated by the Morris water maze test and open-field test.The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments.PubChem,GeneCards,Metascape and other databases were used for targets collection and enrichment analysis.Besides,the association of ingredients targets of DZSM with disease targets of CCH,core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1.Result:The escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment,the crossing times,time spent in the target quadrant,movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment.The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response,phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway,cytokine-cytokine receptor interaction,tumor necrosis factor(TNF)signaling pathway,blood circulation,angiogenesis,extracellular matrix and other related biological processes and pathways,and acting as targets such as interleukin-6(IL-6),TNF,insulin-like growth factor 1(IGF1),vascular endothelial growth factor A(VEGFA),epidermal growth factor(EGF).The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice.Conclusion:DZSM provides a protective effect during CCH,and its multi-component,multi-pathway,multi-target mechanism is also revealed,which provides a basis for further study of the mechanism.
作者
曹光昭
徐核
张毅
周瑞
项昌培
张晶晶
杨洪军
CAO Guang-zhao;XU He;ZHANG Yi;ZHOU Rui;XIANG Chang-pei;ZHANG Jing-jing;YANG Hong-jun(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Chinese Institute for Brain Research,Beijing 102206,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第7期49-56,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家重点研发计划项目(2019YFC1708900)
国家自然科学基金项目(81974550)。
关键词
网络药理学
灯盏生脉胶囊
慢性脑缺血
右侧颈总动脉结扎
药效评价
分子机制
白细胞介素-6(IL-6)
network pharmacology
Dengzhan Shengmai capsules
chronic cerebral hypoperfusion
ligation of right common carotid artery
pharmacodynamic evaluation
molecular mechanism
interleukin-6(IL-6)
