文献类型：期刊文献

中文题名：迷迭香酸甲酯对高原缺氧心肌损伤的保护作用和网络药理学研究

英文题名：The protective effect of methyl rosmarinate on myocardial injury induced by high altitude hypoxia and its network pharmacology study

作者：季前[1,2];孙月梅[1];仇芳芳[1];王延玲[1,2];王荣[1,2];李文斌[1,2]

第一作者：季前

机构：[1]中国人民解放军联勤保障部队第九四〇医院药剂科,甘肃兰州730050;[2]甘肃中医药大学药学院,甘肃兰州730000

第一机构：中国人民解放军联勤保障部队第九四〇医院药剂科,甘肃兰州730050

年份：2025

卷号：41

期号：10

起止页码：1956

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(No 82173738)。

语种：中文

中文关键词：迷迭香酸甲酯;高原;缺氧心肌损伤;网络药理学;分子对接;氧化应激

外文关键词：methyl rosemarinate;plateau;hypoxic myocardial injury;network pharmacology;molecular docking;oxidative stress

摘要：目的探究迷迭香酸甲酯(methyl rosmarinate,MR)对高原缺氧心肌损伤的保护作用及其潜在机制。方法将BALB/c小鼠随机分为对照组、模型组及MR低、中、高剂量组(25、50、75 mg·kg^(-1))。除对照组外,其余组别置于低压低氧舱中,每日腹腔注射给药,持续3 d。实验结束后,取心肌组织进行HE染色观察形态学变化,并测定MDA、GSH、SOD水平评估MR抗心肌损伤活性。通过网络药理学方法预测药物-疾病作用靶点,构建蛋白互作网络(PPI),筛选核心靶点,进行GO功能及KEGG通路富集分析。采用分子对接技术验证MR与核心靶点的结合能力,并通过Westernblot检测相关蛋白表达。结果MR明显减轻高原缺氧引起的心肌损伤。网络药理学分析显示EGFR、Bcl-2、STAT3、MMP9、ESR1、MTOR为核心靶点。分子对接证实MR与核心靶点结合良好。Western blot结果表明MR通过调控STAT3、Bax、Bcl-2蛋白表达改善心肌损伤。结论MR可能通过多靶点机制发挥对高原缺氧心肌损伤的保护作用。
Aim To investigate the protective effects of methyl rosmarinate(MR)on myocardial injury induced by high-altitude hypoxia and explore its underlying mechanisms.Methods BALB/c mice were randomly divided into a control group,a model group,and low-,medium-,and high-dose MR groups(25,50,and 75 mg·kg^(-1),respectively).Except for the control group,all other groups were exposed to a hypobaric hypoxia chamber and administered MR via intraperitoneal injection daily for three days.After the experiment,myocardial tissues were collected for hematoxylin and eosin(HE)staining to observe morphological changes.Levels of malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were measured to evaluate the anti-myocardial injury activity of MR.Network pharmacology was employed to predict drug-disease interaction targets,construct a protein-protein interaction(PPI)network,and identify core targets.Functional enrichment analysis was carried out using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways.Molecular docking was used to verify the binding affinity of MR to core targets,and Western blot was conducted to detect the expression of related proteins.Results MR significantly alleviated myocardial injury caused by high-altitude hypoxia.Network pharmacology analysis identified EGFR,Bcl-2,STAT3,MMP9,ESR1,and MTOR as key targets.Molecular docking confirmed strong binding between MR and these core targets.Western blot results demonstrated that MR improved myocardial injury by regulating the expression of STAT3,Bax,and Bcl-2 proteins.Conclusion MR may exert its protective effects on high-altitude hypoxia-induced myocardial injury through a multi-target mechanism.