AIM To explore the possible mechanism of Dapagliflozin (DAP) in the treatment of diabetes complicated with heart failure from the perspective of cell pyroptosis.
METHOD Thirty rats were randomly divided into control group, model group and DAP group. The diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ) and the heart failure rat model was established by intraperitoneal injection of doxorubicin (DOX). The rats’ spirit, activity, diet and excretion were observed and the cardiac function parameters of rats in each group were detected. The myocardial histopathological results of rats in each group were evaluated by HE, Masson and Sirius red staining. The expression levels of ANP, BNP and BMP-2 in serum of rats in each group were detected by ELISA and the protein levels of BMP-2, NLRP3, csapase-1 and GSDMD in rat myocardial tissue were detected by Western blot. The serum IL-1β and IL-18 expression levels of rats in each group was detected by ELISA.
RESULTS DAP significantly improved the spirit, activity, diet and excretion, decreased the end systolic pressure (P<0.01), heart rate (P<0.05), stroke volume (P<0.01) and ejection fraction (P<0.01) and increased the end diastolic pressure (P<0.01) of rats in the model group. In addition, DAP significantly reduced the fibrotic area of myocardial tissue (P<0.01), decreased the expressions of serum ANP (P<0.01), BNP (P<0.01) and BMP-2 (P<0.01), increased the protein content of BMP-2 (P<0.01) in the myocardial tissue, decreased the protein content of NLRP3 (P<0.01), csapase-1 (P<0.01)and GSDMD (P<0.01) in the myocardial tissue, and decreased the serum IL-1β (P<0.01) and IL-18 (P<0.01) expression levels of the rats in the model group.
CONCLUSION DAP effectively improves myocardial injury in diabetic rats with heart failure and its mechanism may be related to BMP2/NLRP3/Caspase-1 pathway inhibiting cardiomyocyte pyroptosis and reducing myocardial inflammation.
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