Spironolactone alleviates diastolic heart failure by regulating the expression of interleakin-33/soluble tumorigenicity 2 in rats / 中华老年医学杂志

ABSTRACT

Objective:To investigate the effects of Spironolactone on expression of interleukin-33(IL-33)/ suluble tumorigenicity 2(ST2)in a rat model of diastolic heart failure.Methods:Wistar male rats were used to establish a model of diastolic heart failure, which was induced by abdominal aortic coarctation.Rats were randomly divided into the sham operation group, the model group and the Spironolactone group.Rats in the Spironolactone group were given Spironolactone 40 mg/kg/day by intragastric administration, and the sham operation and model groups were given the same amount of physiological saline by intragastric administration for 8 weeks.At the end of the experiment, end-diastolic interventricular wall thickness, left ventricular posterior wall end-diastolic thickness, left ventricular mass and mitral flow E/A were measured via echocardiography.Myocardial tissues were taken and the protein and mRNA expression of soluble ST2(sST2)and IL-33 in rat myocardium was detected by using real-time reverse transcription PCR(RT-PCR)and enzyme-linked immunosorbent assays(ELISA).Results:Compared with the sham operation group, echocardiography showed that end-diastolic interventricular thickness, left ventricular posterior wall end-diastolic thickness and left ventricular mass were increased and mitral flow E/A was decreased in the model group( P<0.05), indicating the model was successful.Compared with the model group, end-diastolic interventricular thickness(2.09±0.11) mm vs.(2.21±0.14) mm, end-diastolic left ventricular posterior wall thickness(2.08±0.17) mm vs.(2.36±0.14) mm and left ventricular mass(0.74±0.17) g vs.(1.35±0.22)g were decreased significantly and the mitral flow E/A ratio(1.44±0.25 vs.1.17±0.13)was elevated in the Spironolactone group( P<0.05), suggesting that spironolactone significantly improved left ventricular diastolic function.RT-PCR and ELISA results showed that sST2 mRNA and protein levels were lower and IL-33 mRNA and protein levels in myocardial tissues were higher in the spironolactone group than in the model group(0.16±0.01) vs.(0.56±0.07), (0.07±0.02)pg/ml vs.(0.35±0.21) pg/ml, (0.67±0.09) vs.0.23±0.05, (0.54±0.11) pg/ml vs.(0.31±0.03) pg/ml, P<0.05. Conclusions:Spironolactone can improve diastolic function in rats by decreasing the expression of sST2 mRNA and protein and enhancing the expression of IL-33 mRNA and protein.