Objective:To study the cardioprotective effect of Baitouwen(Pulsatilla chinensis Regel,PR)in isoproterenol(ISO)induced heart failure in mice,and investigated the molecular targets using network pharmacological predict...Objective:To study the cardioprotective effect of Baitouwen(Pulsatilla chinensis Regel,PR)in isoproterenol(ISO)induced heart failure in mice,and investigated the molecular targets using network pharmacological prediction and experimental validation.Methods:PR were orally administered to ISO induced HF mice for two weeks.The cardiac function was analyzed by echocardiography.Hematoxylin-eosinstaining(HE)was used to evaluate the pathological changes.The PR targets for HF were predicted by bioinformatics analysis tool(BATMAN-TCM).The expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and HF related genes Phosphodiesterase(PDEs),were detected by real-time fluorescence quantitative PCR or Immunohistochemical staining in heart tissues.Results:Cardiac hypertrophy was observed after ISO treatment,and hypertrophic cardiomyocytes were arranged in disorder.Moreover,the expression of ANP and BNP gene in myocardium were upregulated(P<0.05).Treatment of HF mice with PR aqueous extract improved cardiac function characterized by enhanced ejection fraction(EF)and fraction shortening(FS).Furthermore,PR extract also downregulated the expression of ANP and BNP in the heart tissues.Arrangement of cardiomyocytes was also improved.Furthermore,administration of PR group decreased target genes PDE5 and PDE1C expression in the hearts.In addition,PR treatment also improved myocardial fiber distribution and decreased myocardial thickness in the hearts of HF mice.Conclusion:PR treatment may suppress cardiac hypertrophy and improve myocardial function in HF mice via inhibiting the predicted targets PDE5 expression.These results suggest the potential of using PR in preventing the development of HF.展开更多
文摘Objective:To study the cardioprotective effect of Baitouwen(Pulsatilla chinensis Regel,PR)in isoproterenol(ISO)induced heart failure in mice,and investigated the molecular targets using network pharmacological prediction and experimental validation.Methods:PR were orally administered to ISO induced HF mice for two weeks.The cardiac function was analyzed by echocardiography.Hematoxylin-eosinstaining(HE)was used to evaluate the pathological changes.The PR targets for HF were predicted by bioinformatics analysis tool(BATMAN-TCM).The expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and HF related genes Phosphodiesterase(PDEs),were detected by real-time fluorescence quantitative PCR or Immunohistochemical staining in heart tissues.Results:Cardiac hypertrophy was observed after ISO treatment,and hypertrophic cardiomyocytes were arranged in disorder.Moreover,the expression of ANP and BNP gene in myocardium were upregulated(P<0.05).Treatment of HF mice with PR aqueous extract improved cardiac function characterized by enhanced ejection fraction(EF)and fraction shortening(FS).Furthermore,PR extract also downregulated the expression of ANP and BNP in the heart tissues.Arrangement of cardiomyocytes was also improved.Furthermore,administration of PR group decreased target genes PDE5 and PDE1C expression in the hearts.In addition,PR treatment also improved myocardial fiber distribution and decreased myocardial thickness in the hearts of HF mice.Conclusion:PR treatment may suppress cardiac hypertrophy and improve myocardial function in HF mice via inhibiting the predicted targets PDE5 expression.These results suggest the potential of using PR in preventing the development of HF.
