Effect Of Ginsenoside Rb1 On Myocardial Remodeling In Rats With Heart Failure And Its Mechanism

Purpose:To explore the protective effect and mechanism of ginsenoside Rb1 on ventricular remodeling in rats with heart failure.Material and method Thirty male adult SD rats were randomly divided into control group,model group,low dose ginsenoside Rb1 group,high dose ginsenoside Rb1 group and western medicine group.The rat model of heart failure was established by abdominal aortic constriction.Experiment 1: By means of behavior signs observation,Initial body weight,Terminal weight,heart weight,LV(mg)/ BW(g),HR,LVEDP,LVSP,~+LV d P / dt max,-LV d P / dt max and HE staining to evaluate the effections of saponins Rb1 on cardiac function in heart failure rats.Experiment 2: By means of Masson staining,WGA staining,ANF,?-MHC m RNA level and collage I protein content to evaluate the effects of ginsenoside Rb1 on myocardial remodeling in heart failure rats.Experiment 3: By means of peripheral blood Ang ? content,myocardial tissue ACE,AT1 protein content and ACE,AT1 m RNA level to evalua the influence of ginsenoside Rb1 at cycle and local RAS system of heart failure rats,so as to explain the ginsenoside Rb1 neurohumoral mechanisms to improve myocardial remodeling.Experiment 4: By means of the contents of ERK1 / 2,p-ERK1 / 2,TGF-?1 and smad2 / 3 protein in myocardium to evalua the effects of ginsenoside Rb1 on ERK1 / 2,TGF-?1 / Smad2 / 3 signaling pathways so as to explain ginsenoside Rb1 molecular mechanism to improve myocardial remodeling.Results: 1.After 6 weeks of treatment,the symptoms of heart failure in Ginsenoside Rb1 high-dose group and western medicine group improved significantly,the general state was better than control group.2.There was no significant difference in the final body weight between the groups.Compared with the control group,heart weight and heart / body ratios of model group and Rb1 low-dose group were significantly higher than those of control group(P<0.01).Rb1 high-dose group,Western medicine group and the control group has no significant difference.Compared with Abstract model group,the heart weight and heart / body ratio of Rb1 high dose group and western medicine group decreased significantly(P<0.05).3.Parameters of cardiac function :(1)HR: Compared with the control group,the model group was significantly higher(P<0.01);Compared with the model group,Rb1 high dose group and western medicine group decreased significantly(P<0.05);Compared with the Rb1 low dose group,the HR of the Rb1 high dose group and the western medicine group decreased significantly(P<0.05).Compared with the Rb1 low dose group,the western medicine group was significantly decreased(P<0.01);(2)LVSP: Compared with the control group,the model group was significantly lower(P<0.01).Compared with the model group,(3)LVEDP was significantly increased in Rb1 high dose group and western medicine group(P<0.05);Compared with the Rb1 low dose group,the western medicine group was significantly higher(P<0.01);(4)±dp / dtmax: Compared with the control group and the model group,the Rb1 low dose group was significantly decreased(P<0.01);Compared with the model group,Rb1 high dose group and western medicine group higher significantly(P<0.05);Compared with the Rb1 low dose group,the Rb1 high dose group and the western medicine group higher significantly(P<0.05).4.HE staining Histopathology showed:Compared with the model group,the myocardial cells in the treatment group was more regular,the fracture,the defect and the infiltration of inflammatory cell were less than those in the model group.5.WGA staining:Compared with the control group,the myocardial cross-sectional area of model group,Rb1 low-dose group,Rb1 high-dose group and western medicine group were significantly higher(P<0.01);Rb1 low dose group,Rb1 high dose group and western medicine group were significantly lower than those of mode group(P<0.01);Rb1 high dose group and western medicine group were significantly lower than those of Rb1 low dose group(P<0.01).6.Masson staining:The area percentage of collagen of mode group increased significantly compared with the control group;Compared with model group,Rb1 low dose group,Rb1 high dose group and western medicine group were significantly reduced..7.The expression of ANF and ?-MHC m RNA in myocardium:mode group,Rb1 low dose group,Rb1 high dose group and western medicine group were significantly higher than the control group(P<0.05);Rb1 low dose group,Rb1 high dose group and western medicine group were significantly lower than those of mode group(P<0.01);Rb1 high dose group and western medicine group were significantly lower than those of Rb1 low dose group(P<0.01).8.Expression of collagen I protein in myocardium:The expression of collagen I protein in mode group was significantly higher than that in control group(P<0.01);The expression of collagen I protein in Rb1 low dose group was significantly higher than that in control group(P<0.05);The expression of collagen I protein in Rb1 low dose group,Rb1 high dose group and western medicine group were significantly lower compared with the model l group(P<0.01).9.Peripheral blood Ang? content:mode group was significantly higher than that of control group(P<0.01);Rb1 low dose group was significantly higher than that of control group(P<0.05);Rb1 low dose group,Rb1 high dose group and western medicine group were significantly reduced compared with the model group(P<0.01).10.ACE and AT1 Protein content:(1)ACE:Compared with the control group,the model group was significantly higher(P<0.01);Compared with the model group,the high-dose Rb1 group was significantly lower than the model group(P<0.05);Compared with the model group,the western medicine group obviously decreased(P<0.01).Compared Rb1 low dose group,the Rb1 high dose group and the western medicine group lower significantly(P<0.01).(2)AT1: Compared with the control group,the model group was significantly higher(P<0.01);Compared with model group,Rb1 high dose group and western medicine group decreased significantly(P<0.01);Compared Rb1 low dose group,the Rb1 high dose group and the western medicine group lower significantly(P<0.01).11.Expression of ACE and AT1 protein in myocardium:mode group was significantly higher than that of control group(P<0.01);Rb1 high dose group compared with the mode roup,significantly reduced(P<0.05);Compared with the model group,the western medicine group was significantly lower(P<0.01).12.ERK1 / 2 and p-ERK1 / 2 protein conten :(1)ERK1 / 2:There was no statistical significance between the two groups(P>0.05).(2)p-ERK1 / 2:Compared with the control group,the mode group was significantly higher(P<0.01);Rb1 low dose group,Rb1 high dose group and western medicine group were significantly lower than those of mode group(P<0.01).Compared with the Rb1 low dose group,Rb1 high dose group and western medicine group was significantly decreased(P<0.05).13.TGF-?1 and Smad2 / 3 protein content:(1)TGF-?1:Compared with the control group,the model group was significantly higher(P<0.01);Compared with model group,Rb1 high dose group and western medicine group decreased significantly(P<0.01);Compared with the Rb1 low dose group,the western medicine group was significantly reduced(P<0.05).(2)Nucleus Smad2 / 3: Compared with the control group,the model group was significantly higher(P<0.01);Compared with model group,Rb1 high dose group,the Rb1 low dose group and the western medicine group decreased significantly(P<0.01);(3)Cytoplasm Smad2 / 3 : Compared with the control group,the model group was significantly lower(P<0.01);Compared with model group,Rb1 high dose group,the Rb1 low dose group and the western medicine group higher significantly(P<0.01);Conclusion: 1.Ginsenoside Rb1 can improve heart failure rats' symptoms and the cardiac function,inhibit the cardiac remodeling,which has a significant dose-dependent.2.Ginsenoside Rb1 has inhibitory effect on both circulation and local RAS.3.Ginsenoside Rb1 may inhibit cardiac hypertrophy by suppressing the level of Ang ?,reducing ERK activation,affecting ANF,?-MHC m RNA transcription.4.Ginsenoside Rb1 may successively down-regulate the expression of TGF-?1,Smad2 / 3 by inhibiting the level of Ang ?,which lead to the decrease of collagen-? synthesis,and,eventually,suppressing myocardial fibrosis.