| BackgroundChronic heart failure is the end stage of the development of cardiovascular disease, and a serious threat to people’s lives and health, so how to prevent heart failure has been the concern of many scholars. Simvastatin is a classic lipid-lowering drugs. With further research in recent years, the drug has been found that it has pleiotropic effects independent of lipid-lowering effect. It may be beneficial for chronic heart failure, but whether it can be used for the prevention and treatment of heart failure routinely remains controversial, requiring more evidence to support it.ObjectiveBy observing simvastatin intervention in cardiac function of rabbits with heart failure and chromogranin A (CgA) and apoptosis signal-regulated kinase1(ASK1) expression levels in cardiac muscle of rabbits, this study explored the possible mechanisms of simvastatin preventing and treating chronic heart failure, and provided a new evidence for the safety and efficacy of the drug.Methods1.30male rabbits were randomly divided into three groups which include the normal group (n=10), chronic heart failure group (HF group, n=10), simvastatin treatment group (simvastatin group, n=10);2.heart failure model was made by injection of doxorubicin (Adriamycin, ADR) through ear vein, and the normal group were injected with normal saline once a week for12weeks;3.simvastatin group was given simvastatin by gavage once a day for12weeks besides injected with doxorubicin. The other two groups were replaced with the same volume of normal saline;4.continued to observe the animals one week after the treatment was completed, then tested the cardiac ultrasound and hemodynamic parameters of rabbits;5. took the left ventricular myocardial tissue of rabbits, used the HE staining to observe the changes of myocardial cell structure, and took the immune histochemical method to detect the expression of CgA and ASK1, then used real-time PCR method to analysis CgA mRNA and ASK1mRNA expression of myocardial tissue.Results1.cardiac ultrasound results showed that compared with the normal group, heart failure, left ventricular ejection fraction in the simvastatin group (Left ventricular ejection fraction, LVEF) decreased (P<0.01), simvastatin group than in heart failure group (P<0.05); compared with the normal group, heart failure, left ventricular end-diastolic diameter (Left ventricular end diastolic diameter, LVDd) simvastatin group, left ventricular systolic diameter (Left ventricular systolic dimension, LVSd) were increased (P<0.01), simvastatin group than heart failure group (P<0.05); hemodynamic analysis showed that, compared with the normal group, the heart failure group, simvastatin group left ventricular systolic pressure (left ventricular systolic pressure, LVSP) decreased (P<0.05), simvastatin group than heart failure group (P<0.01); compared with the normal group, the heart failure group and simvastatin group maximum rate of rise of left ventricular pressure (pressure maximal rate of rise,+dp/dtmax), the largest rate of decline of left ventricular pressure (Pressure maximal rate of fall,-dp/dtmax) were lower (P<0.01), simvastatin group than heart failure group (P< 0.05).2.HE staining showed:normal cardiomyocytes good shape, arrangement rules, myocardial less fibrous tissue; heart failure, myocardial disorganized, reducing the number of parts of myocardial edema, interstitial fibrous tissue hyperplasia; simvastatin myocardial cells arranged in a more orderly, showing a small amount of fibrous tissue3.1mmunohistochemical method to detect the expression levels of CgA and ASK1of myocardium in each group:the differences of protein expression levels among normal group, heart failure group and simvastatin group were statistically significant; the expressions of CgA and ASKl were increased in heart failure group and simvastatin group compared with the normal group(P<0.01), and the expression in simvastatin group decreased compared with heart failure group(P<0.05).4.Real-time quantitative PCR (Real-time PCR) method to detect the expression levels of CgA mRNA and ASK1mRNA:the expressions of CgA mRNA and ASK1mRNA were increased in heart failure group and simvastatin group compared with the normal group(P<0.01), and the expression in simvastatin group decreased compared with heart failure group(P<0.01).ConclusionSimvastatin is beneficial for chronic heart failure, and its mechanism may be related to inhibition of the expression of CgA and ASK1. |
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