Sitagliptin improves cardiac function after myocardial infarction through activation of autophagy in streptozotocin-induced diabetic mice.

Objective: The aim of this study was to investigate the protective effect of sitagliptin on cardiac function in mice with diabetes and myocardial infarction (MI), and to explore its possible mechanism using the mouse models of diabetes and MI.

Materials And Methods: The models of diabetes and MI were established using C57BL/6 mice. All mice were randomly divided into 5 groups, including the control sham (CS) group, the control MI (CMI) group, the diabetes sham (DS) group, diabetes + MI (DMI) group and the DMI + sitagliptin (DMI+SGL) group. After modeling, mice in the DMI+SGL group were intragastrically administrated with sitagliptin (10 mg/kg/day) for 21 d and the survival rate of mice was recorded. Before and 7, 14, 21 days after MI, the cardiac function of mice in each group was detected via ultrasound. 21 days after MI, the area of MI was measured via 2,3,5-triphenyl tetrazolium chloride (TTC). Meanwhile, the degree of fibrosis in the peripheral region of MI was determined via Masson staining. Moreover, myocardial autophagosomes of mice in each group were observed by transmission electron microscope (TEM). 7 days after MI, the expressions of autophagy-related proteins LC3II and P65 were detected via Western blotting. The expressions of myocardial inflammatory factors, interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). In addition, the expression of nuclear factor-κB (NF-κB) was also detected via Western blotting.

Results: Sitagliptin increased survival rate, improved cardiac function, reduced infarction area, alleviated myocardial fibrosis, enhanced autophagy in the peripheral region and inhibited inflammation in the peripheral region in mice with diabetes after MI.

Conclusions: Sitagliptin can improve cardiac function and reduce the mortality rate in diabetic rats after MI. The possible underlying mechanism may be related to the fact that sitagliptin activates autophagy and inhibits inflammatory response in diabetes after MI.