Ulinastatin inhibits high glucose-induced cardiomyocyte apoptosis through activating Akt signaling.

Abstract

Cardiomyocyte apoptosis is closely associated with the development of diabetic cardiomyopathy. Ulinastatin, a urinary trypsin inhibitor, exerts a protective effect on cardiac function. However, the molecular mechanism remains not fully clear. This study aims to explore the effect of ulinastatin on high glucose (HG)-induced cardiomyocyte apoptosis and the potential molecular mechanism. Neonatal rats cardiomyocytes were cultured and then treated with HG or/and ulinastatin. Cell viability was examined using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Cell apoptosis was detected by flow cytometry. Mitochondrial membrane potential (MMP) was stained using a JC-1 probe and evaluated by fluorescence microscopy. Protein expressions of B-cell lymphoma 2 (Bcl-2) , BCL2-Associated X (Bax), cleaved caspase 3, p-Akt and Akt were determined by Western blot. Ulinastatin increased the HG-induced reduction in cell viability and MMP expression. Ulinastatin also inhibited HG-induced apoptosis. Ulinastatin decreased the Bax/Bcl-2 ratio and cleaved caspase 3 expression in cardiomyocyte treated with HG. Further, ulinastatin increased the phosphorylation level of Akt in cardiomyocyte treated with HG. These effects of ulinastatin were abrogated by LY294002, an Akt inhibitor. Ulinastatin inhibited HG-induced cardiomyocyte apoptosis through activating Akt signaling.