The Effects Of Ginsenosides Rb1 Improving Heart Failure Being Adjusted Via Calcium And Sodium Channels

Objective:Ginsenoside Rb1(GS-Rb1)can enhance myocardial hypoxia tolerance and chemical damage resistance,and also improve cardiac function by regulating calcium "communication" at the cellular level,sarcoplasmic reticulum and mitochondrial level of myocardial cells.Therefore,this study investigated whether GS-Rb1 can improve heart failure(HF)by regulating calcium and sodium channels,and further clarified whether AMPK pathway and/or CaMKⅡ pathway mediate these effects.Methods:After adriamycin(Adr)was successfully used to construct HF model in rats,HF rats were randomly divided into the following 6 groups: HF group(n = 10),Gs-Rb1group(n = 10),AraA group(n = 10),AraA + Gs-Rb1 group(n = 10),KN93 group(n =10)and KN93 + Gs-Rb1 group(n = 10).Left ventricular ejection fraction(LVEF)was measured by two-dimensional echocardiography on the 8th day of the experiment.N-terminal type B natriuretic peptide precursor(NT-proBNP),AMP-dependent protein kinase(AMPK)and calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)activities were measured by ELISA,and mitochondrial reactive oxygen species(mit ROS)levels were measured by DCFH-DA fluorescent probe assay.Western blot was used to detect the expression of L-Type Voltage-Dependent Calcium Channels(LTCC),total LTCC(t-LTCC),Ryanodine Receptor Calcium Release Channel(Ry R2),sarcoplasmic reticulum calcium ATPases(SERCA2a)and calcium sodium exchangers(NCX).Results:1.Gs-Rb1 significantly increased LVEF(P < 0.05)and decreased serum NT pro-BNP level(P < 0.05)in HF rats.AraA significantly inhibited(P < 0.05)the effect of Gs-Rb1 on increasing LVEF in HF rats,but AraA did not significantly affect(P = 0.318)the effect of GS-Rb1 on decreasing NT-Pro BNP.KN93 did not significantly affect(P =0.254)the effect of Gs-Rb1 on increasing LVEF in HF rats,but significantly enhanced(P< 0.05)the effect of GS-Rb1 on decreasing NT-Pro BNP.2.GS-Rb1 significantly enhanced AMPK activity in HF rats(P < 0.05),and AraA almost completely inhibited AMPK activity in HF rats(P < 0.05).KN93 did not affect AMPK activity in HF rats(P =0.302).The effect of GS-Rb1 on increasing AMPK activity was significantly inhibited by AraA(P < 0.05),but not significantly affected by KN93(P = 0.348).3.Gs-Rb1 decreased CaMKⅡ activity in HF rats(P < 0.05),and its effect was significantly enhanced by KN93(P < 0.05),but significantly inhibited by AraA(P < 0.05);the changes of phosphorylated CaMKⅡδ in each group were consistent with the changes of CaMKⅡ activity in each group.4.GS-Rb1 significantly decreased mit ROS content in HF rats(P < 0.05),and its effect was significantly inhibited by AraA(P < 0.05),but not by KN93(P = 0.417).5.There was no significant difference in t LTCC protein expression among the groups(P >0.05);GS-Rb1 group significantly increased p LTCC and RYR2 expression in HF rats(P< 0.01),and these effects were significantly inhibited by AraA(P < 0.05)but not affected by KN93(P > 0.05);p LTCC/LTCC changes in each group were consistent with p LTCC expression in each group.6.GS-Rb1 significantly promoted SERCA2 a expression in HF rats(P < 0.05),which was further enhanced by KN93(P < 0.05),but significantly inhibited by AraA(P < 0.05).7.GS-Rb1 significantly inhibited NCX expression in HF rats(P < 0.05),which was further inhibited by AraA(P < 0.05),but not by KN93(P=0.122).Conclusion:1.Gs-Rb1 significantly improves heart failure.2.Gs-Rb1 may ameliorate heart failure by regulating LTCC redistribution,enhancing Ry R2 expression,increasing SERCA2 a,and inhibiting calcium and sodium channels or transporters such as NCX,and this effect may be mediated by the AMPK pathway and/or the CaMKⅡ pathway.3.Gs-Rb1 may ameliorate heart failure by inhibiting oxidative stress,and the AMPK pathway and/or CaMKⅡ pathway may mediate this effect.