基于斑马鱼模型和网络药理学探究金露梅抗心肌缺血作用机制  

Based on Zebrafish Model and Network Pharmacology to Investigate the Mechanism of Anti-myocardial Ischemia Action of Potentilla Fruticosa L.

作　　者：田雪花 左文明 刘力宽 李锦萍 曾阳 TIAN Xue-hua;ZUO Wen-ming;LIU Li-kuan;LI Jin-ping;ZENG Yang(Qinghai Key Laboratory of Medicinal Plant and Animal Resources,College of Life Sciences,Qinghai Normal University,Xining 810008,China;Plateau Science and Sustainable Development Institute,Xining 810008,China)

机构地区：[1]青海师范大学生命科学学院,青海省药用动植物资源重点实验室,西宁810008 [2]高原科学与可持续发展研究院,西宁810008

出　　处：《科学技术与工程》2025年第3期942-952,共11页Science Technology and Engineering

基　　金：青海省应用基础研究项目(2023-JZ-749);青海省药用植物资源综合利用与开发研究创新项目(2020-2023)。

摘　　要：心肌缺血是因为冠状动脉疾病中心肌耗氧量和氧输送间的不协调引起的,由于其高发病率和死亡率,中国死于缺血性心脏病患者的数量逐年递增。为了验证金露梅有效成分具有抗心肌缺血功效,通过前期试验确定最大耐受浓度(maximum tolerance concentration,MTC)为15.63μg/mL,并依据MTC划分高中低剂量组分别为7.81μg/mL(1/2 MTC)、2.60μg/mL(1/6 MTC)、0.868μg/mL(1/18 MTC),阳性药物组为N-乙酰半胱氨酸(125μg/mL)。借助网络药理学及分子对接技术的方法研究金露梅有效成分抑制心肌细胞凋亡,减缓心肌缺血的可能作用机制。结果表明:借助斑马鱼心脏荧光强度表型图发现金露梅水提物与阳性药物组对比具有明显的防治心肌缺血功效,而且其作用机制与Rap1信号通路、癌症通路、癌症中的蛋白巨糖、PI3K-Akt信号通路、脂质和动脉粥样硬化5条通路有关。可见探究金露梅有效成分的抗心肌缺血机制对防治心肌缺血有一定的理论意义。Myocardial ischemia is caused by the incoordination between myocardial oxygen consumption and oxygen delivery in cor-onary artery disease,and due to its high morbidity and mortality rate,the number of patients who die from ischemic heart disease in China is increasing year by year.In order to verify that the active ingredients of Jinlume have anti-myocardial ischemic efficacy.The maximum tolerated concentration(MTC)was determined to be 15.63μg/mL by the pre-test,and the high school and low dose groups were divided into 7.81μg/mL(1/2 MTC),2.60μg/mL(1/6 MTC)based on the MTC,respectively,0.868μg/mL(1/18 MTC),and the positive drug group was N-acetylcysteine(125μg/mL).With the help of network pharmacology and molecular docking tech-nology,the possible mechanism of action of the active ingredients of Jinlume in inhibiting cardiomyocyte apoptosis and slowing down myocardial ischemia was investigated.The results showed that the aqueous extract of Jinlume had significant effects against myocardial ischemia in comparison with the positive drug group by means of zebrafish cardiac fluorescence intensity phenotyping,and its mecha-nism of action was related to five pathways,namely,Rap1 signaling pathway,cancer pathway,proteoglycans in cancer,PI3K-Akt sig-naling pathway,lipids,and atherosclerosis.It can be seen that exploring the anti-myocardial ischemic mechanism of the active ingredi-ents of Jinlume has certain theoretical significance for the prevention and treatment of myocardial ischemia.

关 键 词：金露梅水提物 斑马鱼 心肌缺血 网络药理学 分子机制 

分 类 号：R285[医药卫生—中药学]