| BackgroundChronic heart failure(CHF)is a complex performance,including hemodynamic changes,the change of metabolism and neurohormonal abnormalities.In the past ten years,despite the rapid development of clinical management,but the number of deaths caused by CHF and rehospitalization is still soaring.Changes in the internal structure of the left ventricle may contribute to the development of heart failure.At the cellular level,CHF showed endothelial dysfunction,increased inflammation and oxidative stress,cell migration and apoptosis.ObjectiveTo study the effect of simvastatin on silent mating type information regulation 2homolog-2(SIRT2)/nuclear factor-κB(NF-κB)signaling pathway in rabbits with chronic heart failure is through the establishment of chronic heart failure rabbit model,and the drug simvastatin intervention.MethodsTwenty-four New Zealand male rabbits were randomly divided into normal group,chronic heart failure(CHF)group and simvastatin group,eight rabbits in each group.The rabbits in the CHF group and simvastatin group were daily injected with adriamycin through ear vein to establish CHF models.The normal group were injected with the same dose of saline injection.At the same time,the simvastatin group were treated with 1.5mg · kg-1 simvastatin by intragastric administration daily,and in the normal group and CHF group were treated with the same dose of physiological saline by intragastric administration daily.All the rabbits were dealt for twelve weeks.The heart function of therabbits in the groups was observed by ultrasonography at the end of modeling.The rabbits were sacrificed and the left ventricles were made into paraffin embedded sections.The histological changes of myocardium were observed by hematoxylin eosin staining.The expression of SIRT2 and NF-κB protein in myocardial tissue of rabbits in the groups was detected by immunohistochemical method.The expression of SIRT2 mRNA and NF-κB mRNA was detected by reverse transcription polymerase chain reaction.Results1 In the process of modeling,there was no death in the New Zealand rabbits in the normal group.,three New Zealand rabbits died in the CHF group,,two New Zealand rabbits died in the simvastatin group.Morphological and histological of heart were performed in the survival New Zealand rabbits of each group.The results show that:In the normal group,the myocardial cells of the New Zealand white rabbits were arranged in order,the cell space was normal,and the nucleus was clear.In the CHF group,the cardiac muscle fibers were arranged in disorder,some of them were even broken,the cell nucleus were abnormal,some cells showed edema and vacuolar degeneration,and myocardial cell gap widened significantly.Compared with the CHF group,the edema and vacuolar degeneration of myocardial cells in the New Zealand white rabbits of the simvastatin group,The myocardial fibers were arranged more orderly in the simvastatin group.2 Cardiac ultrasound results showed that:Compared with the normal group,the left ventricular ejection fraction(LVEF)of rabbits was significantly decreased(P<0.01),and the left ventricular end diastolic dimension(LVDd)of rabbits was significantly increased in the simvastatin group and CHF group(P<0.01).Compared with the CHF group,the LVEF of rabbits was significantly increased(P<0.01),and the LVDd of rabbits was significantly decreased in the simvastatin group(P<0.01).3 Immunohistochemical results showed that:The positive expression rate of SIRT2 protein in myocardial cells of rabbits in CHF group was significantly lower than that in normal group(P<0.01).The positive expression rate of SIRT2 protein in myocardial cellsof rabbits in simvastatin group was significantly higher than that in normal group and CHF group(P<0.01).The positive expression rate of NF-κ B protein in myocardial cells of rabbits in CHF group was significantly higher than that in normal group(P<0.01).The positive expression rate of NF-κ B protein in myocardial cells of rabbits in simvastatin group was significantly lower than that in normal group and CHF group(P<0.01).4 Reverse transcription polymerase chain reaction results showed that:The relative expression of SIRT2 mRNA in myocardial cells of rabbits in CHF group was significantly lower than that in normal group(P<0.05).The relative expression of SIRT2 mRNA in myocardial cells of rabbits in simvastatin group was significantly higher than that in normal group and CHF group(P<0.01).The relative expression of NF-κ B mRNA in myocardial cells of rabbits in CHF group was significantly higher than that in normal group(P<0.01).The relative expression of NF-κ B mRNA in myocardial cells of rabbits in simvastatin group was significantly lower than that in normal group and CHF group(P<0.01).ConclusionSimvastatin can inhibit myocardial apoptosis.and improve cardiac function of rabbits,which may be inhibit the expression of NF-κB by up-regulating the expression of SIRT2 in myocardial cells of rabbits,... |
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