基于网络药理学和实验验证探讨参附汤对心源性休克的作用机制  

Mechanism of action of Shen-Fu decoction on cardiogenic shock based on network pharmacology and experimental validation

作　　者：徐敬娅 张春蕾[2] 李宝龙 XU Jing-ya;ZHANG Chun-lei;LI Bao-long(School of Basic Medicine,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Jiamusi College,Heilongjiang University of Traditional Chinese Medicine,Jiamusi,Heilongjiang 154007,China;Drug Safety Evaluation Center,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040 [2]黑龙江中医药大学佳木斯学院,黑龙江佳木斯1540072 [3]黑龙江中医药大学药物安全性评价中心,黑龙江哈尔滨150040

出　　处：《中国药理学通报》2023年第8期1548-1557,共10页Chinese Pharmacological Bulletin

基　　金：黑龙江省自然科学基金面上项目(No H2015017);哈尔滨市科技创新人才研究专项基金项目(青年后备人才计划项目)(No 2016RAQYJ186)。

摘　　要：目的基于网络药理学及动物实验探讨参附汤防治心源性休克的作用机制。方法通过网络药理学预测参附汤作用心源性休克的相关靶点和信号通路;以冠状动脉结扎法制造心源性休克大鼠模型,造模前大鼠根据分组给予相应剂量的参附汤或生理盐水灌胃14 d,建模成功后记录大鼠实时平均动脉压变化。HE法检测心源性休克大鼠心肌组织病理学改变;TUNEL法检测大鼠心肌细胞凋亡程度;Western blot法测定大鼠心肌组织Bax、Bcl-2、caspase-3、cleaved caspase-3蛋白表达水平。结果网络药理学最终筛选出参附汤潜在活性成分51种,参附汤与心源性休克共同作用靶点80个,核心靶点43个,GO富集分析显示核心蛋白参与的生物途径(biology process,BP)涉及凋亡过程正调节,KEGG富集分析显示涉及动脉粥样硬化、凋亡相关信号通路。动物实验验证结果显示,参附汤能够升高心源性休克大鼠血压,减轻心肌组织病理学改变;减轻大鼠心肌细胞凋亡程度,降低大鼠心肌组织caspase-3、cleaved caspase-3、Bax蛋白表达水平,提高Bcl-2蛋白表达水平。结论参附汤的潜在活性成分可能通过作用靶点Bax、Bcl-2调控心肌细胞凋亡信号通路,从而起到对心源性休克大鼠的防治作用。Aim To investigate the mechanism of action of Shen-Fu decoction in the prevention and treatment of cardiogenic shock based on network pharmacology and animal experiments.Methods The relevant targets and signaling pathways of cardiogenic shock of Shen-Fu decoction were predicted by network pharmacology,and a cardiogenic shock rat model was created by coronary artery ligation.Before modeling,rats were given the appropriate dose of Shen-Fu decoction or saline by gavage for 14 days according to the group,and real-time mean arterial pressure(MAP)changes were recorded after successful modeling.HE method was used to detect the myocardial histopathological changes of cardiogenic shock.TUNEL method was employed to detect rat myocardial cell apoptosis,and Western blotting was applied to determine the expression levels of rat myocardial Bax,Bcl-2,caspase-3,cleaved caspase-3 proteins.Results A total of 51 potential active ingredients of Shen-Fu decoction were screened out by network pharmacology,80 targets of co-action with cardiogenic shock,and 43 core targets of close relationship between proteins,and GO enrichment analysis revealed that the core proteins were involved in the biology process(BP),mainly involving positive regulation of apoptotic process.KEGG enrichment analysis showed signaling pathways involving atherosclerosis-related,apoptosis and other signaling pathways.The results of animal model validation showed that Shen-Fu decoction could increase the shock blood pressure of rats with cardiogenic shock and alleviate the pathological changes of myocardial tissue,reduce the degree of apoptosis of rat cardiomyocytes,reduce the expression level of caspase-3,cleaved caspase-3 and Bax protein in rat myocardial tissue,and improve the expression level of Bcl-2 protein in myocardial tissue of rats.Conclusions The potential active ingredient of Shen-Fu decoction may play a role in the prevention and control of cardiogenic shock rats by acting on the target Bax,Bcl-2 to regulate the apoptosis signaling pathway of cardiomyocy

关 键 词：参附汤 心源性休克 网络药理学 BAX BCL-2 凋亡 

分 类 号：R-332[医药卫生] R289.5R319R329.25R542.22