Effect of Sacubitril/Valsartan on RhoA-ROCK Signaling Pathway to Ventricular Remodeling in Rats with Chronic Heart Failure
Objective:To analyze the regulation of sacubitril/valsartan to the RhoA-ROCK signaling pathway in rat with chronic heart failure(CHF),and the effect of ventricular remodeling.Methods:A total of 45 SD rats were divided into 3 groups randomly,which were control group(injected normal saline),model group(made CHF rat model by peritoneal injection with Adriamycin)and therapy group(intragastric administration sacubitril/valsartan with 60 mg/kg 4 weeks to CHF rats).Each group had 15 rats.The cardiac function indexes of left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDD),interventricular septal thickness(IVST),left ventricular mass index(LVMI)and the plasma levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),matrix metal-loproteinase-9(MMP-9),Galectin-3(Gal-3)were compared among 3 groups.The cardiac histomorphology indexes and degree of my-ocardial collagen deposition were detected and compared among 3 groups.The expression levels of RhoA and ROCK in myocardial tis-sue were compared among 3 groups.Results:The LVEF of rats in control group were highest,and the LVEF of rats in therapy group were higher than in model group(P＜0.05).The levels of LVEDD,IVST,LVMI in control group were lowest,and the levels of LVEDD,IVST,LVMI in therapy group were lower than model group(P＜0.05).The plasma levels of NT-proBNP,MMP-9,Gal-3 in control group were highest,and the levels of NT-proBNP,MMP-9,Gal-3 in therapy group were higher than model group(P＜0.05).The enlarged car-diac cell and disorderly arrangement in model group were observed,and the degrees of myocardial collagen deposition in model group were larger than therapy group.The expression levels of RhoA and ROCK of myocardial tissue were different among 3 groups,which the indexes in control group were the lowest,and the therapy group was the second lowest,and the model group was the highest(P＜0.05).The positive relationship of the expression levels of RhoA and ROCK to the levels of LVEDD,IVST,LVMI,NT-proBNP,MMP-9 and Gal-3 were confirmed(P＜0.05),and the negative relationship to LVEF was also confirmed(P＜0.05).Conclusion:Sacubitril/valsartan has significant negative effect on the ventricular remodeling by the RhoA-ROCK signaling pathway in CHF.
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