基于网络药理学和实验验证探索红花减轻小鼠心脏低温冷保存过程心肌损伤的作用机制  

Exploring the Mechanism of Safflower in Alleviating Myocardial Injury during Low-Temperature Storage of Mouse Hearts Based on Network Pharmacology and Experimental Verification

作　　者：王俊壹[1] 王寒 林超[1] WANG Junyi;WANG Han;LIN Chao(School of Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Department of Science and Technology,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学医学院,江苏南京210023 [2]南京中医药大学科学技术处,江苏南京210023

出　　处：《南京中医药大学学报》2025年第2期233-242,共10页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81903927);江苏省研究生培养创新工程研究生科研与实践创新计划(KYCX21_1727)。

摘　　要：目的探索红花对低温冷保存的小鼠心脏的保护机制,分析红花潜在的作用靶点,为中药红花改善离体心肌损伤提供参考。方法借助TCMSP、TCMID、Swiss Target Prediction等数据库检索红花的化学成分和作用靶点。通过OMIM、TTD、Genecards等数据库筛选出缺血性心肌病(Ischemic cardiomyopathy,ICM)的疾病靶点。使用Cytoscape构建“药物-成分-靶点-疾病”网络图,富集分析红花作用机制。构建小鼠离体心脏冷保存模型,采用ELISA检测、qPCR、Western blot等技术手段验证网络药理学的预测靶点。结果共获得红花活性成分22个、药物靶点421个;ICM 1812个疾病靶点,得到药物-疾病共同靶点117个,GO富集分析共得到条目1906个,KEGG通路富集筛选出包括Akt信号通路在内的共计137条信号通路。实验验证红花可能通过调节PI3K-Akt通路调控细胞凋亡过程、炎症进程从而减轻小鼠心脏在低温冷保存过程中受到的损伤。结论运用网络药理学揭示了红花对小鼠低温冷保存心脏的保护作用靶点和通路,并进行了相关实验验证,为深入探讨红花减轻低温冷保存心脏心肌损伤的作用机制提供了依据,为红花的临床应用和药理研究提供理论基础。OBJECTIVE To explore the protective mechanism of safflower on mouse hearts preserved at low temperatures,summarize and analyze the potential targets of safflower,and provide reference for the improvement of ex vivo myocardial injury by traditional Chinese medicine safflower.METHODS Databases such as TCMSP,TCMID,and Swiss Target Prediction were used to search for the chemical composition and target of safflower.Databases such as OMIM,TTD,and Genecards were employed to screen disease targets for ischemic cardiomyopathy.A network diagram of“drug-ingredient-target-disease”was construct using Cytoscape,and the mechanism of the action of safflower was enriched and analyzed.A mouse ex vivo heart cold preservation model was constructed and the predicted targets of network pharmacology were validated using techniques such as ELISA detection,qPCR,Western blot,etc.RESULTS A total of 22 active ingredients and 421 drug targets were obtained from safflower;1812 disease targets were identified in ischemic cardiomyopathy,resulting in 117 drug-disease common targets.GO enrichment analysis yielded 1906 entries,and KEGG pathway enrichment screening identified a total of 137 signaling pathways,including the Akt signaling pathway.Experimental verification showed that safflower might alleviate the damage to mouse hearts during low-temperature storage by regulating the PI3K-Akt pathway to regulate cell apoptosis.CONCLUSION This article uses network pharmacology to reveal the protective targets and pathways of safflower on the heart of mice subjected to low-temperature cold storage,and conducts relevant experimental verification.This provides a basis for further exploring the mechanism of safflower in reducing myocardial injury in low-temperature cold stored hearts,and provides a theoretical basis for the clinical application and pharmacological research of safflower.

关 键 词：红花 网络药理学 心肌损伤 冷保存 PI3K-AKT 

分 类 号：R285.5[医药卫生—中药学]