基于网络药理学和转录组学探讨活心丸防治心力衰竭机制  

Mechanism Study on Huoxin Pill in the Prevention and Treatment of Heart Failure Based on Network Pharmacology and Transcriptomics

作　　者：刘想 陈科翰 郑楚瑶 廖弈秋 王羚郦[1] LIU Xiang;CHEN Kehan;ZHENG Chuyao;LIAO Yiqiu;WANG Lingli(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Baiyunshan Pharmaceutical General Factory,Guangzhou Baiyunshan Pharmaceutical Holdings Co.,Ltd.,Guangzhou 510515,China)

机构地区：[1]广州中医药大学中药学院,广州510006 [2]广州白云山医药集团股份有限公司白云山制药总厂,广州510515

出　　处：《医药导报》2025年第3期377-386,共10页Herald of Medicine

基　　金：广州市科技计划项目(202103000049)。

摘　　要：目的基于网络药理学和转录组学分析探讨活心丸(HXP)防治心力衰竭(HF)的作用机制。方法将小鼠随机分为正常对照组,模型对照组,阳性对照组(沙库巴曲缬沙坦钠,60 mg·kg^(-1)),HXP小、大剂量组(31.2,62.4 mg·kg^(-1));其他组皮下注射异丙肾上腺素(ISO)(5 mg·kg^(-1))造模,正常对照组灌胃等量无菌0.9%氯化钠溶液;6 h后各给药组灌胃相应药物,正常对照组与模型对照组灌胃等体积无菌水,连续21 d。彩色多普勒超声成像系统检测小鼠心功能;酶联免疫吸附测定(ELISA)法测定血清环磷酸腺苷(cAMP)、N端B型利钠肽原(NT-proBNP)及B型利钠肽(BNP)水平;苏木精-伊红(HE)染色和马松(Masson)染色法评价心肌组织病理形态,计算胶原容积分数(CVF);网络药理学结合转录组学预测HXP防治HF潜在靶点和信号通路,采用分子生物学手段进行验证。结果与正常对照组比较,模型对照组左室收缩末期内径(LVESd)及左室舒张末期内径(LVEDd)增大(P<0.01),左室射血分数(LVEF)和左室短轴缩短率(LVFS)降低(P<0.01),血清BNP、NT-proBNP、cAMP含量上升(P<0.01),心肌组织间胶原纤维增多,CVF值升高(P<0.01)。与模型对照组比较,HXP小、大剂量组和阳性对照组LVESd、LVEDd下降(P<0.01),LVEF、LVFS上升(P<0.01);血清BNP、NT-proBNP、cAMP水平下降(P<0.05);心肌组织纤维化程度减轻,CVF下降(P<0.01)。网络药理学与转录组学联合分析,共预测出HXP防治HF关键靶点10个:CACNA1H、SCN10A、FGF12、PVALB、ACAN、LGALS3、SERPINE1、MMP3、GSTM1、VDR。蛋白免疫印迹法结果显示,与正常对照组比较,模型对照组心肌组织蛋白激酶A(PKA)和cAMP反应元件结合蛋白(CREB)蛋白活化水平升高(P<0.01);与模型对照组比较,HXP小、大剂量组和阳性对照组心肌组织PKA、CREB蛋白活化水平下降(P<0.05)。结论HXP对ISO所致小鼠HF具有改善作用,该作用可能涉及众多靶点及cAMP/PKA信号通路。Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg^(-1)),low-dose group treated with HXP(31.2 mg·kg^(-1)),and high-dose group treated with HXP(62.4 mg·kg^(-1)).The model control group and each drug treatment group were subcutaneously injected with an equal volume of ISO(5 mg·kg^(-1))for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P<0.01),and a decrease in LVEF and LVFS(P<0.01);BNP,NT-proBNP,and cAMP levels were increased(P<0.01);myocardial collagen fibers increased and CVF increased(P<0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P<0.01),and an increase in LVEF and LVFS(P<0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P<0.05);the degree of myocardial fibrosis decreased and CVF decreased(P<0.01).Network pharmacology combine

关 键 词：活心丸 心力衰竭 网络药理学 转录组学 环磷酸腺苷/蛋白激酶A信号通路 

分 类 号：R285.5[医药卫生—中药学] R714.252[医药卫生—中医学]