基于网络药理学及实验验证探究保元汤对ISO诱导的慢性心力衰竭大鼠的治疗作用  

Therapeutic effect of Baoyuan Decoction on ISO-induced chronic heart failure in rats based on network pharmacology and experimental validation

作　　者：刘星彤 陆莉宏 董俊秀 张玉珊 刘莉[1] 齐滨[1] LIU Xingtong;LU Lihong;DONG Junxiu;ZHANG Yushan;LIU Li;QI Bin(School of Pharmaceutical Sciences,Changchun University of Chinese Medicine,Jilin Changchun 130117,China)

机构地区：[1]长春中医药大学药学院,吉林长春130117

出　　处：《中国医院药学杂志》2024年第19期2205-2214,2222,共11页Chinese Journal of Hospital Pharmacy

基　　金：“十四五”国家重点研发计划(编号:2021YFD1600903-02);吉林省大学生创新创业训练计划项目(编号:S202210199026X)。

摘　　要：目的:基于指纹图谱-网络药理学-分子对接技术及实验验证探究保元汤对异丙肾上腺素(ISO)诱导的慢性心力衰竭大鼠模型的治疗作用。方法:采用高效液相色谱法建立保元汤物质基准指纹图谱并进行含量测定;运用网络药理学构建“活性成分-作用靶点-疾病”网络,进行GO富集分析和KEGG通路富集分析,利用Autodock Tools软件对关键活性成分和关键靶点进行分子对接验证,初步确定保元汤治疗慢性心力衰竭的活性成分及潜在机制;采用ISO剂量梯度递减法建立SD大鼠慢性心力衰竭模型,分组后给予相应药物灌胃4周,期间观察记录大鼠的各项指标;给药结束后对大鼠进行解剖,进行心肌酶相关因子检测、心肌组织病理学及免疫组织化学实验等操作。结果:建立的10批保元汤物质基准指纹图谱相似度均大于0.900,表明所建立的指纹图谱方法可对保元汤进行鉴定和质量控制;网络药理学结果显示保元汤中5个关键活性成分,11个关键靶点,涉及细胞对化学应激的反应、糖尿病并发症中的AGE-RAGE信号通路、细胞凋亡等主要通路;分子对接结果显示保元汤中关键化合物槲皮素、山柰酚、异鼠李素与所有关键靶点均有较强烈的结合活性;心脏系数、ELisa试剂盒及HE、Masson染色结果均显示相同结果,即造模后出现明显心肌损伤,证明造模成功,给药组损伤减轻,低剂量组未见显著差异,高剂量组效果显著优于低剂量组,与模型组相比有显著差异。免疫组化结果显示,ISO造模组较空白组出现显著的Bax和Caspase-3蛋白表达增多,Bcl-2表达下降,低剂量组改善效果不显著,高剂量给药组均可降低Bax和Caspase-3的表达,提高Bcl-2的表达。结论:该研究初步揭示了保元汤有效成分通过多靶点调控、参与多种信息通路和生物学过程治疗慢性心力衰竭的作用机制。OBJECTIVE To explore the therapeutic effect of Baoyuan Decoction(BYD)on isoproterenol(ISO)-induced chronic heart failure(CHF)rats based upon fingerprinting-network pharmacology-molecular docking technique and experimental validations.METHODS High performance liquid chromatography(HPLC)was utilized for establishing the baseline fingerprints and determining the contents of BYD.Network pharmacology was employed for constructing the"active ingredient-target-disease"network,GO enrichment analysis and KEGG pathway enrichment analysis and molecular docking validation of key active ingredients and key targets.Using Autodock Tools software,the authors initially determined the active ingredient and the potential therapeutic mechanism of BYD for CHF.CHF model of Sprague-Dawley rats was established by ISO dose gradient decreasing method.The rats were grouped and received the corresponding drugs by a 4-week gavage.All parameters were recorded.The animals were sacrificed at the end of drug dosing.The samples were subjected to the detection of cardiac enzyme-related factors,myocardial histopathology and immunohistochemistry.RESULTS The similarity of baseline fingerprints of 10 batches of BYD was greater than 0.900.It indicated that the established fingerprint method could be used for identification and quality control of BYD.The network pharmacology results showed 5 key active ingredients and 11 key targets in BYD,involving the major signaling pathways of cellular responses to chemical stress and AGE-RAGE in diabetic complications and apoptosis.Molecular docking results showed that quercetin,kaempferol and isorhamnetin and key compounds in BYD had potent binding activities with all key targets.The results of cardiac weight index,enzyme-linked immunosorbent assay(ELISA)kit and hematoxylin-eosin/Masson stain showed the same results of marked myocardial injury after modeling.It proved that modeling was successful and injury lessened in dosing group.There was no significant difference in low-dose group.The efficacy of high-dose gro

关 键 词：保元汤 慢性心力衰竭 指纹图谱 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学] R965[医药卫生—中医学]