文献类型：期刊文献

中文题名：基于网络药理学和实验验证探讨当归红芪超滤物对放射性心脏病的作用机制

英文题名：Study on the Mechanism of Action of Radix Angelica Sinensis and Radix Hedysari Ultrafiltration on Radiation-induced Heart Disease Based on Network Pharmacology and Experimental Verification

作者：魏惠平[1,2];李淑玲[1];王倩[1];马承旭[3];靳佩[1];沈彦萍[1]

第一作者：魏惠平

机构：[1]甘肃中医药大学附属医院,甘肃兰州730020;[2]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730000;[3]兰州大学第一医院,甘肃兰州730099

第一机构：甘肃中医药大学第二附属医院

年份：2024

卷号：38

期号：8

起止页码：89

中文期刊名：实用中医内科杂志

外文期刊名：Journal of Practical Traditional Chinese Internal Medicine

基金：甘肃省自然科学基金项目(21JR7RA581);甘肃省中医药管理局项目(GZKZ-2020-09)。

语种：中文

中文关键词：网络药理学;实验验证;当归红芪超滤物;放射性心脏病;作用机制

外文关键词：network pharmacology;experimental verification;Radix Angelica Sinensis and Radix Hedysari Ultrafiltration;radiation-induced heart disease;mechanism of action

摘要：目的 基于网络药理学和动物实验探讨当归红芪超滤物(RAS-RH)防治放射性心脏病(RIHD)的潜在机制。方法 利用中药系统药理学数据库与分析平台(TCMSP)数据库遴选“当归-红芪”的活性成分及预测干预靶点。在GeneCards、人类孟德尔遗传数据库(OMIM)检索RIHD靶点蛋白,采用R软件整合共同靶点,利用STRING数据库构建药物成分-疾病交集靶点蛋白互作网络(PPI),并R软件对PPI结果进行可视化分析;运用R软件与Bioconductor平台对将成分-疾病交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。将Wistar雄性大鼠40只,随机分为空白组、模型组、中药组、西药组,除空白组外其余各组采用X线(10Gy)单次辐射诱导构建RIHD大鼠模型,饲养30 d后持续给药4周,采用ELISA法检测给药4周后各组大鼠血清中肌钙蛋白I、脑钠肽水平,Western Blot检测预测的核心靶标半胱氨酸天冬氨酸蛋白酶(Caspase)-3、白介素(IL)-6、人表皮生长因子受体(EGFR)在各组大鼠心肌组织中的表达。结果 网络药理学分析:RAS-RH的主要活性成分16个、对应靶标210个,药物与疾病交集靶标58个;GO富集1792个条目(P<0.05),其中生物过程(BP)1559个条目、细胞组分(CC)38个条目、分子功能(MF)95个条目;KEGG通路富集分析共筛选出135条信号通路(P<0.05),主要涉及致癌-受体激活信号通路、脂质和动脉粥样硬化信号通路、流体剪切应力和动脉粥样硬化、癌症中的蛋白聚糖、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、肿瘤坏死因子(TNF)、缺氧诱导因子(HIF)-1等信号通路。动物实验:ELISA检测结果提示模型组大鼠血清cTnI、BNP显著升高,与模型组相比药物组cTnI、BNP显著降低(P<0.05);Western Blot检测结果提示:模型组大鼠心肌组织Caspase-3、IL-6蛋白表达升高、EGFR蛋白表达降低,与模型组相比药物组Caspase-3、IL-6降低、EGFR蛋白表达升高(P<0.05)。结论 当归红芪超滤物的有效成分主要通过作用HIF-1α、MYC、Caspase-3、EGFR、IL-6、CCND1、VEGFA等核心靶点调节PI3K/Akt、TNF、HIF-1等信号通路从而发挥防护RIHD的作用,为中药抗辐射研究提供一定的参考。
Objective To investigate the potential mechanism of Radix Angelica Sinensis and Radix Hedysari Ultrafiltration(RAS-RH) in the prevention and treatment of Radiation-induced Heart Disease(RIHD) based on network pharmacology and animal experiments. Methods The active components and predicted intervention targets of "Angelica sinensis-Radix Hedysari " were selected using the database of Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP). Retrieve RIHD target proteins in GeneCards and Human Mendelian Inheritance Database(OMIM), use R software to integrate common targets, use STRING database to construct drug component-disease intersection target protein interaction network(PPI), and use R software to compare PPI results Perform visual analysis;use R software and Bioconductor platform to conduct Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of component-disease intersection targets. Forty male Wistar rats were randomly divided into blank group, model group, traditional Chinese medicine group, and western medicine group. Except for the blank group, the other groups were induced by X-ray(10Gy) single radiation to establish the RIHD rat model, and the rats were kept for 30 days. After 4 weeks of administration, ELISA was used to detect serum levels of troponin I and brain natriuretic peptide in each group after 4 weeks of administration, and Western Blot detected the predicted core target caspase-3. The expression of interleukin(IL)-6 and human epidermal growth factor receptor(EGFR) in myocardial tissue of rats in each group.Results Network pharmacology analysis: RAS-RH had 16 main active components, 210 corresponding targets, and 58 drug-disease intersection targets;GO enriched 1792 items(P<0.05), of which 1559 were biological processes(BP). 38 items, cellular component(CC), 95 molecular function(MF) items;KEGG pathway enrichment analysis screened out a total of 135 signaling pathways(P<0.05), mainly involving oncogenic-receptor activation signaling pathway, lipid Plasma and atherosclerosis signaling pathways, fluid shear stress and atherosclerosis, proteoglycans in cancer, phosphatidylinositol 3-kinase(PI3K)/Akt(protein kinase B), tumor necrosis factor(TNF), hypoxia-inducible factor(HIF)-1 and other signaling pathways. Animal experiments: The results of ELISA showed that the serum cTnI and BNP of the rats in the model group were significantly increased, and compared with the model group, the cTnI and BNP of the drug group were significantly decreased(P<0.05).-3. The expression of IL-6 protein was increased, and the expression of EGFR protein was decreased. Compared with the model group, Caspase-3 and IL-6 in the drug group were decreased, and the expression of EGFR protein was increased(P<0.05). Conclusion The effective components of Radix Angelica Sinensis and Radix Hedysari Ultrafiltration mainly regulate PI3K/Akt, TNF, HIF-1 and other signaling pathways by acting on core targets such as HIF-1α, MYC, Caspase-3, EGFR, IL-6, CCND1, and VEGFA. In this way, it can play the role of protecting RIHD and pass certain reference for the research on anti-radiation of traditional Chinese medicine.