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作 者:陈晶晶 周亚滨[2] 贺粤 黄超 张文风[1] CHEN Jing-jing;ZHOU Ya-bin;HE Yue;HUANG Chao;ZHANG Wen-feng(Basic Medical College,Changchun University of Chinese Medicine,Changchun 130117,China;The Second Dept of Cardiovascular,the First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150006,China;Dept of Traditional Chinese Medicine,Shenzhen Bao′an District People′s Hospital,Shenzhen Guangdong 518000,China)
机构地区:[1]长春中医药大学基础医学院,吉林长春130117 [2]黑龙江中医药大学附属第一医院心血管二科,黑龙江哈尔滨150006 [3]深圳市宝安区人民医院中医科,广东深圳518000
出 处:《中国药理学通报》2025年第5期942-950,共9页Chinese Pharmacological Bulletin
基 金:国家自然科学基金资助项目(No 81903985);长春中医药大学“杏林学者工程-青年科学家项目”培养计划(No QNKXJ2-2021ZR20);深圳市宝安区医疗卫生科研项目(No 2023JD256)。
摘 要:目的基于网络药理学及动物实验验证探讨养心汤治疗慢性心力衰竭(chronic heart failure,CHF)的作用机制。方法采用数据库对养心汤进行筛选,建立“药物-成分-疾病-靶点”的网络,对得到的靶标进行富集分析。采取腹主动脉结扎术复制大鼠CHF模型,给药结束后,观察大鼠一般状况及体质量、心脏重量,测定血流动力学变化、心脏超声指标、左心室质量指数;HE染色观察心肌组织形态学变化;ELISA检测血清IL-1β、IL-18、TNF-α、BNP;Western blot检测NLRP3、caspase-1、ASC及NF-κB p65蛋白表达情况。结果富集分析得出养心汤治疗CHF的潜在调控通路涉及NOD-like信号通路、NF-κB信号通路等;动物实验结果显示,给药组大鼠体质量、左心室舒张期内径、左心室收缩期内径降低(P<0.05),左心室质量指数、射血分数、短轴缩窄率升高(P<0.05),心肌组织病理形态减轻,IL-1β、IL-18、TNF-α、BNP及NLRP3、caspase-1、ASC、NF-κB p65蛋白水平下降(P<0.05)。结论养心汤治疗CHF大鼠的作用机制可能与抑制NLRP3炎症小体信号通路活化,减轻炎症反应有关。Aim To explore the mechanism of Yangxin decoction in the treatment of chronic heart failure(CHF)based on network pharmacology and animal experiments.Methods The database was used to screen Yangxin decoction,a network of“drug-component-disease-target”was established,and the obtained targets were enriched and analyzed.The CHF model of rats was replicated by abdominal aortic ligation.After the administration,the general condition,body weight and heart weight of the rats were observed,and the hemodynamic changes,echocardiography indicators and left ventricular mass index were measured.HE staining was used to observe the morphological changes of myocardial tissue.Serum IL-1β,IL-18,TNF-αand BNP were detected by ELISA.The expressions of NLRP3,caspase-1,ASC and NF-κB p65 proteinswere detected by Western blot.Results Enrichment analysis showed that the potential regulatory pathways of Yangxin decoction in the treatment of CHF involved NOD-like signaling pathway,NF-κB signaling pathway,etc.The results of animal experiments showed that the body weight,left ventricular diastolic diameter and left ventricular systolic diameter of the rats in the administration group decreased(P<0.05),the left ventricular mass index,ejection fraction and short axis narrowing rate increased(P<0.05),the pathological morphology of myocardial tissue was reduced,and the levels of IL-1β,IL-18,TNF-α,BNP,NLRP3,caspase-1,ASC and NF-κB p65 decreased(P<0.05).Conclusions The mechanism of Yangxin decoction in the treatment of CHF rats may be related to inhibiting the activation of NLRP3 inflammasome signaling pathway and reducing the inflammatory response.
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